VII. 2. References

The complete bibliography of "MicroBiota Handbook" — the original scientific sources behind the reference numbers that appear in the chapters.

What is in the bibliography?

This appendix holds the book's complete bibliography in one place: every scientific reference cited in any chapter of the volume. The `[12]`, `[325]` and other numbers in the body text point to the entries listed below — the numbering runs across the entire book, so the same `[N]` reference number always points to the same source. The vast majority of the listed publications appeared in peer-reviewed journals and are also findable in indexed databases (PubMed/NCBI, Crossref), from reputable professional publishers.

Why is there a summary under each entry?

Under each reference there is a 5–6 sentence synopsis. This is not the article's official abstract but a short, plain-language summary presenting the study's background, the method used, the main result, and its clinical or practical significance. Its purpose is to let the reader quickly decide whether the full publication is worth reading and whether it fits their own question or the patient's situation. The summaries help you orient yourself even without direct access to the full text.

How to use it?

Under each entry you will find the "Cited in" line: clicking the chapter number shown there returns you to the part of the book where the source is cited. Within that chapter, clicking the `[N]` marker brings the reader here, to the bibliography — so you can move freely in both directions. Clicking the reference marked "Link" opens the publication on the publisher's or NCBI's site, where — if the article is freely accessible (open access) — the full text can also be read.

References

[7] van Nood E, Vrieze A, Nieuwdorp M et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013. Link

Open-label RCT in patients with recurrent C. difficile infection comparing duodenal donor faeces infusion (after short vancomycin + bowel lavage) with standard 14-day vancomycin, with or without bowel lavage. The primary endpoint was diarrhoea resolution without relapse at 10 weeks. The trial was stopped early at interim analysis: 13/16 patients (81\%) in the FMT arm achieved resolution after a single infusion, substantially exceeding both vancomycin arms. Establishes FMT as superior to antibiotic monotherapy for recurrent CDI and provides the landmark evidence base for FMT clinical translation.

[16] Sinha R, Abu-Ali G, Vogtmann E et al. Assessment of Variation in Microbial Community Amplicon Sequencing by the Microbiome Quality Control (MBQC) Project Consortium. Nature Biotechnology. 2017. Link

The Microbiome Quality Control (MBQC) baseline study assessed taxonomic profiling variability across 15 laboratories and 9 bioinformatics protocols using blinded stool, chemostat and artificial community specimens. Variability depended most on biospecimen type and origin, followed by DNA extraction, sample handling environment and bioinformatics pipeline. Artificial community analyses revealed quantitative differences in extraction efficiency and bioinformatic classification. The findings highlight the need for standardisation to enable meta-analysis of population-scale microbiome studies.

[18] Gloor GB, Macklaim JM, Pawlowsky-Glahn V, Egozcue JJ. Microbiome datasets are compositional: and this is not optional. Front Microbiol. 2017. Link

Microbiome datasets generated by high-throughput sequencing of 16S rRNA amplicons, metagenomes or metatranscriptomes are inherently compositional because the instrument imposes an arbitrary total. The review explains the pathologies that arise when compositional data are analysed with non-compositional methods and provides guidance for applying compositional data analysis throughout microbiome study workflows. The compositional framework is presented as essential, not optional, for valid inference.

[19] Costea PI, Zeller G, Sunagawa S et al. Towards Standards for Human Fecal Sample Processing in Metagenomic Studies. Nature Biotechnology. 2017. Link

21 representative DNA extraction protocols were tested on identical faecal samples and compared with library preparation and storage effects against biological within-individual variation. DNA extraction had the largest technical effect on metagenomic outcomes. Protocols were ranked by DNA quantity, quality, and biases in community diversity and Gram-positive/Gram-negative ratio. The authors recommend a standardised, transferable DNA extraction method validated using a mock community of known composition for human faecal metagenomic studies.

[21] McLaren MR, Willis AD, Callahan BJ. Consistent and Correctable Bias in Metagenomic Sequencing Experiments. eLife. 2019. Link

Marker-gene and metagenomic sequencing measurements are systematically biased toward detecting certain taxa over others, making taxon abundances generated by different protocols quantitatively incomparable and prone to spurious biological conclusions. The authors propose a mathematical model of experimental bias based on real-experiment properties and validate it with 16S rRNA and shotgun metagenomics data from defined bacterial communities. The model fits experimental data better than previous, more complex frameworks and offers a path to correcting bias.

[22] Sczyrba A, Hofmann P, Belmann P et al. Critical Assessment of Metagenome Interpretation -- A Benchmark of Metagenomics Software. Nature Methods. 2017. Link

The Critical Assessment of Metagenome Interpretation (CAMI) challenge benchmarked metagenomics software using highly complex realistic datasets from ~700 newly sequenced microorganisms and ~600 novel viruses and plasmids. Assembly and binning performed well for species represented by individual genomes but were substantially degraded by closely related strains. Taxonomic profiling and binning were proficient at high taxonomic ranks with a marked drop below family level. Parameter settings strongly affected performance, underscoring the importance of reproducibility. CAMI provides a roadmap for software selection.

[28] Vétizou M, Pitt JM, Daillère R et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015. Link

The antitumour effect of CTLA-4 blockade depends on specific Bacteroides species. In mice and patients, T-cell responses against B. thetaiotaomicron or B. fragilis correlated with treatment efficacy. Antibiotic-treated or germ-free mice did not respond to anti-CTLA-4, and the defect was rescued by B. fragilis gavage, polysaccharide immunisation, or transfer of B. fragilis-specific T cells. Faecal microbiota transplantation from humans to mice confirmed that CTLA-4 therapy in melanoma patients favours outgrowth of B. fragilis with anticancer activity.

[36] Cammarota G, Ianiro G, Tilg H et al. European consensus conference on faecal microbiota transplantation in clinical practice. Gut. 2017. Link

European consensus conference developing evidence-based recommendations on FMT for clinical practice, with 28 experts from 10 countries collaborating in working groups. Statements were generated through evidence-based review, evaluated electronically via a Delphi process, and finalized in a plenary consensus session. Recommendations cover FMT indications, donor selection, faecal material preparation, clinical management, faecal delivery, and minimum requirements for establishing an FMT centre. Provides the European standardization framework for safe and governed FMT delivery.

[59] Thaiss CA, Zeevi D, Levy M et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell. 2014. Link

Mechanistic study in mice and humans demonstrating that the gut microbiota exhibits diurnal oscillations driven by feeding rhythms, producing time-specific compositional and functional profiles. Disruption of host molecular clock components or jet lag caused aberrant microbiota oscillations and dysbiosis through impaired feeding rhythmicity. Jet-lag-induced dysbiosis in both species promoted glucose intolerance and obesity that were transferable by FMT to germ-free recipients. Identifies microbiota–host circadian cross-regulation as a metabolic disease mechanism.

[60] Benedict C, Vogel H, Jonas W et al. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Mol Metab. 2016. Link

Randomized within-subject crossover study in 9 normal-weight men comparing two nights of partial sleep deprivation (PSD; 02:45–07:00) with two nights of normal sleep (22:30–07:00) under standardized in-lab meal and exercise conditions. Faecal samples were collected and oral glucose tolerance was tested. The study assessed whether short-term sleep loss alters gut microbiota composition and metabolic function, providing early human evidence linking sleep restriction to acute microbiota shifts and insulin resistance.

[62] Clarke SF, Murphy EF, O'Sullivan O et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014. Link

Cross-sectional 16S rRNA amplicon study comparing gut microbiota composition in professional rugby athletes with control groups matched for physical size, age and gender. Athletes showed higher microbial diversity and distinct community structure linked to both extreme exercise and accompanying dietary differences. Provides early evidence that elite-level exercise and diet jointly shape the gut microbiota, supporting downstream investigations into the exercise–diet–microbiome triad in metabolic and immune health.

[93] Goldenberg JZ, Yap C, Lytvyn L et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017. Link

Systematic review of probiotics for primary prevention of Clostridium difficile-associated diarrhoea in adults receiving antibiotics. The review evaluates efficacy and safety against the backdrop of guideline recommendations that do not endorse probiotic prophylaxis despite high-quality probiotic evidence. The synthesis supports probiotic prophylaxis as effective and safe in appropriately selected hospitalized adults on antibiotics.

[106] Wastyk HC, Fragiadakis GK, Perelman D et al. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021. Link

17-week randomized prospective trial (n=18/arm) in healthy adults comparing high-fibre versus high-fermented-food diets with multi-omics microbiome and host immune profiling. The high-fibre diet increased microbiome-encoded glycan-degrading CAZymes despite stable diversity. The high-fermented-food diet increased microbiome diversity and decreased multiple inflammatory markers. Findings demonstrate diet-specific microbiome–immune effects and support fermented foods as a strong, diversity-promoting modulator of the gut–immune axis.

[122] Costantini L, Molinari R, Farinon B, Merendino N. Impact of Omega-3 Fatty Acids on the Gut Microbiota. Int J Mol Sci. 2017. Link

Long-term dietary habits shape host-specific gut microbiota, but dietary fat effects are less well characterised than those of carbohydrates. The few adult human omega-3 PUFA supplementation studies show consistent changes: decreased Faecalibacterium, increased Bacteroidetes and butyrate-producing Lachnospiraceae. Because dysbiosis of these taxa occurs in inflammatory bowel disease, omega-3 PUFAs may exert a beneficial effect by restoring microbial composition and increasing anti-inflammatory short-chain fatty acid production.

[141] David LA, Maurice CF, Carmody RN et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014. Link

Short-term consumption of diets composed entirely of animal versus plant products produced dramatic, reproducible shifts in human gut microbial community structure that overwhelmed inter-individual differences. The animal-based diet increased bile-tolerant microbes (Alistipes, Bilophila, Bacteroides) and decreased plant-polysaccharide-fermenting Firmicutes (Roseburia, E. rectale, R. bromii), mirroring herbivore-vs-carnivore patterns. Bilophila wadsworthia bloomed on the animal-based diet, mechanistically linking dietary fat, bile acids and the outgrowth of microbes capable of triggering inflammatory bowel disease.

[154] Suez J, Korem T, Zeevi D et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014. Link

Non-caloric artificial sweeteners (NAS) induced glucose intolerance in mice and humans via compositional and functional changes in the gut microbiota. Antibiotic treatment abrogated the deleterious metabolic effects, and germ-free mice receiving faecal transplants from NAS-consuming mice (or NAS-incubated microbiota) developed glucose intolerance. NAS-altered microbial metabolic pathways were linked to metabolic disease susceptibility, with similar dysbiosis and glucose intolerance demonstrated in healthy human subjects. The findings call for reassessment of widespread NAS use.

[159] Chassaing B, Koren O, Goodrich JK et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015. Link

In wild-type mice, relatively low concentrations of two ubiquitous emulsifiers — carboxymethylcellulose (CMC) and polysorbate-80 (P80) — induced low-grade inflammation and obesity/metabolic syndrome, and promoted robust colitis in mice predisposed to it. The mucus-protective barrier and microbiota composition were disrupted. The findings implicate dietary emulsifiers, ubiquitous components of processed foods, in the post-mid-20th-century rise in inflammatory bowel disease and metabolic disorders.

[161] Desai MS, Seekatz AM, Koropatkin NM et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016. Link

In gnotobiotic mice colonised with a synthetic human gut microbiota, chronic or intermittent dietary fibre deficiency caused the microbiota to use host-secreted mucus glycoproteins as a nutrient source, eroding the colonic mucus barrier. Combined fibre deprivation and a mucus-eroding microbiota allowed greater epithelial access and lethal colitis by the mucosal pathogen Citrobacter rodentium. The findings link diet, microbiome and intestinal barrier dysfunction and identify dietary fibre as a key barrier-protective factor exploitable for therapeutic strategies.

[162] Suez J, Cohen Y, Valdés-Mas R et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022. Link

Randomised controlled trial in 120 healthy adults receiving saccharin, sucralose, aspartame or stevia (in doses below acceptable daily intake) versus glucose-vehicle or no supplement for 2 weeks. All four non-nutritive sweeteners distinctly altered the stool/oral microbiome and plasma metabolome; saccharin and sucralose significantly impaired glycaemic responses. Gnotobiotic mice colonised with microbiomes from top and bottom human responders reproduced donor-specific glycaemic responses, demonstrating that non-nutritive sweeteners can induce person-specific, microbiome-dependent glycaemic alterations.

[172] Halmos EP, Power VA, Shepherd SJ, Gibson PR, Muir JG. A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Gastroenterology. 2014. Link

Randomised single-blind cross-over trial in 30 IBS patients and 8 controls compared a low-FODMAP diet (<0.5 g/meal) with a typical Australian diet for 21 days each (>=21-day washout). Almost all food was provided. The low-FODMAP arm produced significantly greater reduction in IBS symptoms measured on 0-100 mm visual analogue scales, supporting the low-FODMAP diet as an effective intervention for symptom control in IBS compared with a standard Western diet.

[204] Allen JM, Mailing LJ, Niemiro GM et al. Exercise alters gut microbiota composition and function in lean and obese humans. Med Sci Sports Exerc. 2018. Link

This 6-week endurance training trial in 32 previously sedentary lean (n=18) and obese (n=14) adults assessed exercise-induced changes in gut microbiota composition, function and metabolite output, followed by a 6-week sedentary washout. Training progressed from 30 to 60 minutes at 60-75% of HR reserve, three days per week. Beta-diversity analysis showed that exercise-induced microbiota alterations were dependent on obesity status. The findings indicate that endurance training reshapes the gut microbiota in a host-phenotype-dependent manner, with effects partly reversible upon return to inactivity.

[213] Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012. Link

This review synthesizes evidence that the gut microbiota influences brain function and behaviour via neural, endocrine and immune pathways. Germ-free animals and models of pathogen infection, probiotics or antibiotics implicate gut bacteria in the regulation of anxiety, mood, cognition and pain. The microbiota-gut-brain axis emerges as a tractable target for developing novel therapeutics for complex CNS disorders. The authors call for translational studies establishing causal links in humans.

[218] Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA. 2011. Link

This longitudinal study examined the distal gut microbiota of three individuals over 10 months spanning two courses of ciprofloxacin, analyzing 1.7 million 16S rRNA sequences from 52-56 samples per subject. Interindividual variation dominated; baseline within-subject communities were stable over months. Ciprofloxacin profoundly reduced diversity and shifted composition within 3-4 days of initiation, with incomplete and individual-specific recovery. The findings characterize gut microbiota resilience and the durable disruption caused by repeated fluoroquinolone exposure.

[222] Forslund K, Hildebrand F, Nielsen T et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015. Link

Using 784 human gut metagenomes, this study disentangled type 2 diabetes (T2D) microbiome signatures from antidiabetic drug effects and showed antidiabetic medication, particularly metformin, confounds prior T2D dysbiosis associations. The authors provide evidence for microbial mediation of metformin's therapeutic effects through short-chain fatty acid production, and for microbiota-mediated mechanisms behind known GI side effects, including a relative increase in Escherichia species. The findings highlight that treatment status must be controlled when characterizing disease-associated microbiomes.

[229] Maier L, Pruteanu M, Kuhn M et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018. Link

This in vitro screening tested >1000 marketed drugs against 40 representative gut bacterial strains and found that 24% of human-targeted drugs across all therapeutic classes inhibited at least one strain. Antipsychotics were overrepresented in this group. Drug effects on gut bacteria correlated with antibiotic-like side effects in humans and matched existing cohort data. Susceptibility to antibiotics and human-targeted drugs correlated across species, indicating shared resistance mechanisms verified for several drugs. The findings raise concern that non-antibiotics may promote antibiotic resistance.

[234] Routy B, Le Chatelier E, Derosa L et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018. Link

This translational study showed that primary resistance to PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in advanced cancer can be attributed to abnormal gut microbiome composition, with antibiotics reducing ICI clinical benefit. FMT from ICI responders into germ-free or antibiotic-treated mice restored PD-1 blockade efficacy; nonresponder FMT did not. Stool metagenomics correlated ICI response with Akkermansia muciniphila abundance. Oral A. muciniphila after nonresponder FMT restored PD-1 efficacy via IL-12-dependent CCR9+CXCR3+CD4+ T-cell recruitment. The findings establish microbiome modulation as an adjunct to cancer immunotherapy.

[238] Dominguez-Bello MG, Costello EK, Contreras M et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA. 2010. Link

This study used multiplexed 16S rRNA pyrosequencing to characterize bacterial communities from 10 mother-newborn dyads (4 vaginal, 6 cesarean deliveries), sampling mothers' skin, oral and vaginal sites pre-delivery and neonatal skin, oral, nasopharyngeal aspirate and meconium within 24 hours. Delivery mode strongly shaped neonatal microbiota establishment across all body habitats: vaginally born infants harboured communities resembling maternal vaginal microbiota, while C-section infants resembled maternal skin. The findings document the foundational influence of delivery mode on the initial human microbiome.

[300] Goodrich JK, Waters JL, Poole AC et al. Human genetics shape the gut microbiome. Cell. 2014. Link

This study compared microbiotas across >1000 fecal samples from the TwinsUK population, including 416 twin pairs, to test host-genetic effects on the gut microbiome. Many microbial taxa showed heritable abundance, most notably the family Christensenellaceae, which formed a co-occurrence network with other heritable Bacteria and methanogenic Archaea. Christensenellaceae and its partners were enriched in individuals with low body mass index. The findings provide population-scale evidence that host genetics shapes the gut microbiome and interacts with it to influence metabolic phenotype.

[306] Mirzayi C, Renson A, Genomic Standards Consortium et al. Reporting Guidelines for Human Microbiome Research: The STORMS Checklist. Nature Medicine. 2021. Link

This methodological consensus from multidisciplinary microbiome researchers adapted observational and genetic epidemiology reporting guidelines into the Strengthening The Organization and Reporting of Microbiome Studies (STORMS) tool. STORMS is a 17-item checklist organized into six sections matching typical publication structure, with new elements for laboratory, bioinformatics and statistical analyses specific to culture-independent microbiome studies. The findings provide a standardized reporting framework facilitating manuscript preparation, peer review, reader comprehension and comparative analysis of microbiome studies.

[381] Househam AM, Peterson CT, Mills PJ, Chopra D. The effects of stress and meditation on the immune system, human microbiota, and epigenetics. Adv Mind Body Med. 2017. Link

Househam, Peterson, Mills and Chopra's 2017 Advances in Mind-Body Medicine review examines effects of stress and meditation on the immune system, human microbiota and epigenetics. The authors synthesise evidence that chronic psychological stress activates HPA-axis cortisol release, autonomic dysregulation, and pro-inflammatory cytokine production, with documented dysbiotic shifts in gut microbiota (decreased Lactobacillus and Bifidobacterium, increased pathobionts). Conversely, meditation practices — mindfulness, yoga, transcendental meditation — show effects on telomere length, DNA methylation, inflammatory gene expression and microbiota composition. The review supports a gut-brain-immune-mind axis framework and motivates trials of mind-body interventions for stress-related microbiome dysfunction.

[382] Zeb F, Wu X, Chen L et al. Effect of time-restricted feeding on metabolic risk and circadian rhythm associated with gut microbiome in healthy males. Br J Nutr. 2020. Link

This study examined the effects of time-restricted feeding (TRF) on metabolic markers, circadian rhythm and gut microbiota in healthy adult males. Subjects were allocated to TRF (n=56) or non-TRF (n=24) groups for a 25-day trial. Blood was sampled pre-TRF and post-TRF (TRF group) or once at 25 days (non-TRF). Serum lipid and liver profiles were measured; real-time PCR assessed circadian and inflammatory gene expression. TRF improved serum lipid profile and liver markers, modulated circadian and inflammatory gene expression in a direction consistent with metabolic benefit, and produced gut microbiota-linked rhythm changes. The findings support TRF as a non-pharmacological strategy aligning eating-window with circadian biology to reduce metabolic risk.

[402] Feuerstadt P, Louie TJ, Lashner B et al. SER-109, an Oral Microbiome Therapy for Recurrent Clostridioides difficile Infection. New England Journal of Medicine. 2022. Link

This phase III RCT (ECOSPOR III) tested SER-109, an oral microbiome therapeutic of purified Firmicutes spores, in adults with ≥3 CDI episodes (inclusive of the qualifying acute episode). After standard-of-care antibiotics, patients received SER-109 or placebo (4 capsules daily for 3 days). Diagnosis required toxin testing at trial entry, with stratification by age and antibiotic. The primary efficacy endpoint was reduced risk of CDI recurrence at 8 weeks. SER-109 achieved significant superiority over placebo for sustained clinical response. Analyses also documented microbiome engraftment and shifts in microbial metabolites consistent with the spore-formulation mechanism. The trial supported FDA approval of SER-109 (Vowst) as the first oral microbiome therapeutic for recurrent CDI.

[476] Marotz CA, Sanders JG, Zuniga C et al. Improving Saliva Shotgun Metagenomics by Chemical Host DNA Depletion. Microbiome. 2018. Link

To enable shotgun metagenomic sequencing of host-dominated oral samples, three commercial host-depletion kits, size filtration, and a novel osmotic-lysis + propidium-monoazide method (lyPMA) were compared in human saliva. lyPMA was the most efficient method, reducing host-aligned reads from 89,29 ± 0,03% in untreated samples to 8,53 ± 0,10%. Furthermore, lyPMA-treated samples showed the lowest taxonomic bias compared with untreated controls. The method is recommended for microbial-DNA enrichment from host-rich oral samples in metagenomic studies.

[504] Gionchetti P, Rizzello F, Helwig U et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003. Link

Gionchetti and colleagues' 2003 Gastroenterology paper is the landmark double-blind, placebo-controlled trial of the VSL#3 probiotic for prophylaxis of pouchitis onset after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis. Forty post-IPAA UC patients were randomized for one year to VSL#3 (a blend of four Lactobacillus, three Bifidobacterium and Streptococcus thermophilus strains) or placebo. Pouchitis occurred in 10% of the VSL#3 group versus 40% on placebo (p<0.05), with significantly better quality of life on the probiotic. The trial established VSL#3 as grade-A evidence for pouchitis prevention in the ECCO and AGA guidelines.

[505] Bin-Nun A, Bromiker R, Wilschanski M et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. 2005. Link

Neonates ≤1500 g were randomized to either daily feeding supplementation with a probiotic mixture (Bifidobacterium infantis, Streptococcus thermophilus, Bifidobacterium bifidus; 10^9 CFU/day) or no supplement. Birth weight, gestational age and time to full feeds did not differ between 72 study and 73 control infants. The incidence of necrotizing enterocolitis (NEC) was significantly reduced in the probiotic group (4% vs. 16,4%; p=0,03), and NEC severity by Bell's criteria was lower (2,3 ± 0,5 vs. 1,3 ± 0,5; p=0,005). Prophylactic probiotics reduce both NEC incidence and severity in very-low-birth-weight infants.

[506] Sokol H, Pigneur B, Watterlot L et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008. Link

Mucosa-associated microbiota was profiled in Crohn's disease (CD) patients at surgical resection and 6 months later by FISH. A reduction of Faecalibacterium prausnitzii — a major Firmicutes member — was associated with higher risk of postoperative ileal CD recurrence; lower F. prausnitzii on resected ileal mucosa also correlated with endoscopic recurrence at 6 months. In vitro and in vivo (TNBS-induced colitis) experiments demonstrated anti-inflammatory effects of F. prausnitzii. The species is a potential biomarker for postoperative recurrence risk and a candidate therapeutic in CD.

[507] Costello SP, Hughes PA, Waters O et al. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA. 2019. Link

A multicenter, randomized, double-blind trial in three Australian centers enrolled 73 adults with mild-to-moderate ulcerative colitis. Patients received anaerobically prepared pooled donor FMT (n=38) or autologous FMT (n=35) via colonoscopy followed by 2 enemas over 7 days, with 12-month follow-up. Anaerobic stool processing was hypothesized to enhance microbial viability and allow efficacy with shorter, less intensive FMT therapy. The trial supports anaerobically prepared, short-duration FMT as an effective induction therapy in active UC.

[508] Camilleri, M. Diagnosis and treatment of irritable bowel syndrome: a review. JAMA. 2021. Link

Irritable bowel syndrome (IBS) affects 7–16% of the US population, most often women and young adults, with direct annual costs over USD 1 billion. Diagnosis has traditionally been symptom-based. Validation studies of consensus symptom-based criteria favor simpler identification of the cardinal symptoms (abdominal pain, bowel dysfunction, bloating) and exclusion of alarm symptoms (unintentional weight loss, rectal bleeding, recent change in bowel function). Diagnostic accuracy is enhanced by additional history, physical examination including digital rectal examination, and basic screening tests (hemoglobin, C-reactive protein) to exclude organic disease.

[510] Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2015. Link

Several studies indicate altered gut microbiota composition and function in celiac disease — alterations that may precede disease onset and/or persist on a gluten-free diet. The microbiota may promote or attenuate celiac-associated immunopathology. The review summarizes current evidence linking host genetics, environmental factors and intestinal microbiota in disease pathogenesis, and highlights the importance of animal models (using gnotobiotic technology) and long-term clinical studies to define cause-effect relationships and to evaluate microbiota-modulation as a therapeutic or preventive strategy.

[511] Kostic AD, Chun E, Robertson L et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013. Link

Fusobacterium spp. were enriched in human colonic adenomas relative to surrounding tissues, and in stool of colorectal adenoma and carcinoma patients versus healthy subjects. In the ApcMin/+ mouse model, F. nucleatum increased tumor multiplicity and selectively recruited tumor-infiltrating myeloid cells, promoting tumor progression. Tumors from F. nucleatum-exposed mice shared a proinflammatory signature with human Fusobacterium-positive colorectal carcinomas. Unlike other CRC-linked bacteria, F. nucleatum did not exacerbate colitis or inflammation-associated carcinogenesis, suggesting a distinct, myeloid-driven mechanism.

[513] Davar D, Dzutsev AK, McCulloch JA et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021. Link

A clinical trial evaluated responder-derived FMT combined with anti-PD-1 in PD-1-refractory melanoma patients. The combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid, durable microbiota perturbation. Responders showed increased abundance of taxa previously linked to anti-PD-1 response, increased CD8+ T-cell activation, and decreased IL-8-expressing myeloid cells. Distinct proteomic and metabolomic signatures, plus transkingdom network analyses, confirmed gut microbiome regulation of these immune changes. FMT can overcome resistance to PD-1 blockade in melanoma.

[514] Walters WA, Xu Z, Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 2014. Link

A consistent IBD microbiota signature was identified across multiple cohorts that allowed high-accuracy classification of IBD vs. non-IBD subjects when 16S rRNA data were re-analyzed with a common pipeline. By contrast, although individuals could be classified as lean or obese with significant accuracy within each cohort — consistent with experimental phenotype transfer — signatures of obesity were not consistent between studies, even with harmonized analysis. Results indicate that microbe-condition correlations with smaller effect sizes (obesity) require different cohort and analysis strategies than larger ones (IBD).

[515] Vrieze A, Van Nood E, Holleman F et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology. 2012. Link

Male recipients with metabolic syndrome were randomized to small-intestinal infusion of allogeneic (lean-donor) or autologous gut microbiota. Six weeks after lean-donor infusion, insulin sensitivity increased (median glucose disappearance rate: 26,2 → 45,3 μmol/kg/min; p<0,05), with parallel increase in butyrate-producing intestinal microbiota. The proof-of-concept study supports development of gut microbiota as a therapeutic agent to improve insulin sensitivity in humans.

[516] Aron-Wisnewsky J, Vigliotti C, Witjes J et al. Gut microbiota and human NAFLD: disentangling microbial signatures from metabolic disorders. Nat Rev Gastroenterol Hepatol. 2020. Link

Gut microbiota dysbiosis is repeatedly reported in obesity and type 2 diabetes, both strongly linked with non-alcoholic fatty liver disease (NAFLD). Animal studies suggest a potential causal role of gut microbiota in NAFLD. Human studies have begun to identify microbiome signatures discriminating healthy individuals from those with NAFLD, NASH or cirrhosis, but metabolic confounders are not always accounted for. Heterogeneous lesions, demographic variability and differing sequencing/diagnostic methods may explain discrepant findings, indicating need for standardized, well-controlled future studies.

[517] Stiemsma LT, Reynolds LA, Turvey SE, Finlay BB. The hygiene hypothesis: current perspectives and future therapies. ImmunoTargets Ther. 2015. Link

Developed countries have seen a steady increase in atopic and immune-dysregulation disorders since the 1980s, paralleled by a decrease in infectious diseases. The original 'hygiene hypothesis' (Strachan 1989) has been expanded over the past decade into the 'microflora' and 'old friends' hypotheses, linking commensal microbiota and parasitic helminths with normal immune development. Current evidence supports the potential of manipulating intestinal microbiota to treat or prevent atopic disease, IBD and type 1 diabetes, and underscores the co-evolution of human immunity with microbial and parasitic partners.

[518] Parodi A, Paolino S, Greco A et al. Small intestinal bacterial overgrowth in rosacea: clinical effectiveness of its eradication. Clin Gastroenterol Hepatol. 2008. Link

In 113 consecutive rosacea outpatients (31 M / 82 F; mean age 52 ± 15 years) and 60 sex- and age-matched healthy controls, lactulose and glucose breath tests assessed small intestinal bacterial overgrowth (SIBO). SIBO-positive patients were randomized to rifaximin 1200 mg/day for 10 days or placebo; a SIBO-negative subgroup also received rifaximin. Eradication was assessed 1 month after therapy. The trial supports a clinically relevant association between SIBO and rosacea and the effectiveness of rifaximin-mediated SIBO eradication in improving rosacea symptoms.

[519] Kang DW, Adams JB, Coleman DM et al. Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Sci Rep. 2019. Link

Open-label 2-year follow-up of an 18-participant Microbiota Transfer Therapy (MTT) trial — combining antibiotics, bowel cleanse, stomach-acid suppressant and FMT — in children with autism spectrum disorder. Most GI improvements were maintained, and autism-related symptoms improved further after end of treatment. Key microbiota changes (significantly increased bacterial diversity and relative abundance of Bifidobacterium and Prevotella) persisted at follow-up. Findings support the durable safety and benefits of FMT-based MTT in ASD.

[520] Sampson TR, Debelius JW, Thron T et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016. Link

In α-synuclein-overexpressing mice modeling Parkinson's disease, gut microbiota were required for motor deficits, microglia activation and α-synuclein pathology. Antibiotic treatment ameliorated, and microbial re-colonization promoted, pathophysiology in adult animals — indicating that postnatal gut-brain signaling modulates disease. Oral administration of specific microbial metabolites to germ-free mice promoted neuroinflammation and motor symptoms. The findings establish a functional link between gut bacteria and synucleinopathies and suggest microbiota-targeting as a therapeutic strategy in PD.

[521] Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019. Link

A random-effects meta-analysis of 34 controlled clinical trials evaluated prebiotic and probiotic effects on depression and anxiety. Prebiotics did not differ from placebo for depression (d=-0,08; p=0,51) or anxiety (d=0,12; p=0,11). Probiotics produced small but significant effects for depression (d=-0,24; p<0,01) and anxiety (d=-0,10; p=0,03). Sample type moderated probiotic effect on depression, with a larger effect in clinical/medical samples (d=-0,45; p<0,001) than community samples; a preliminary restricted analysis of psychiatric samples yielded medium-to-large effect (d=-0,73; p<0,001).

[522] Dominy SS, Lynch C, Ermini F et al. Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019. Link

Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, and its toxic gingipain proteases were identified in Alzheimer's disease (AD) brains, with gingipain levels correlated to tau and ubiquitin pathology. Oral P. gingivalis infection in mice colonized the brain and increased Aβ1-42 production. Gingipains were neurotoxic in vitro and in vivo, damaging tau. Small-molecule gingipain inhibitors reduced brain P. gingivalis load, blocked Aβ1-42 production, attenuated neuroinflammation and rescued hippocampal neurons — supporting gingipain inhibition as a therapeutic strategy in AD.

[523] Scher JU, Sczesnak A, Longman RS et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013. Link

Rheumatoid arthritis (RA) is a systemic autoimmune disease driven by genetic and environmental factors. The authors performed 16S sequencing on 114 stool samples (RA patients and controls) plus shotgun sequencing on a subset of 44. Prevotella copri was strongly correlated with disease in new-onset untreated RA (NORA); increased Prevotella abundance correlated with reduced Bacteroides and loss of reportedly beneficial microbes. Unique Prevotella genes also correlated with disease. Findings link expansion of P. copri to early RA pathogenesis and suggest microbiota-based biomarkers and therapeutic targets.

[524] Vaziri ND, Yuan J, Khazaeli M et al. Disintegration of colonic epithelial tight junction in uremia. Am J Nephrol. 2013. Link

In a rat CKD model (0,7% adenine chow for 2 weeks), oral activated charcoal AST-120 (4 g/kg/day for 2 weeks) was tested for its hypothesized capacity to adsorb urea and urea-derived ammonia and thereby mitigate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. CKD impairs intestinal barrier function, allowing systemic influx of noxious products. The study supports AST-120 as a therapeutic strategy to preserve epithelial tight junctions and reduce systemic inflammation in CKD by modifying the gut chemical environment.

[525] Pasini E, Aquilani R, Testa C et al. Pathogenic gut flora in patients with chronic heart failure. JACC Heart Fail. 2016. Link

60 stable, well-nourished chronic heart failure (CHF) patients (NYHA I–II n=30; NYHA III–IV n=30) plus 20 matched healthy controls underwent stool culture for bacteria and fungi (Candida), intestinal permeability (cellobiose sugar test), echocardiographic right atrial pressure (RAP) measurement, and CRP measurement. The study correlates pathogenic gut flora and intestinal permeability with disease severity, venous blood congestion and inflammation in CHF, supporting the hypothesis that gut-flora translation/translocation contributes to systemic inflammation in CHF.

[526] Anand S, Mande SS. Diet, microbiota and gut-lung connection. Front Microbiol. 2018. Link

Gut microbiota influences metabolic and immune homeostasis. Diet is a major determinant of its composition and the metabolites it produces, which modulate gastrointestinal immunity and impact distal organs such as lung and brain. Micro-aspiration of gut bacteria and migration of sensitized immune cells through lymph or blood may also shape organ-specific immune responses. Dysbiosis has been implicated in lung diseases including allergy, asthma and cystic fibrosis, supporting a gut–lung axis as a therapeutic target in respiratory disease.

[541] Knight R, Vrbanac A, Taylor BC et al. Best practices for analysing microbiomes. Nat Rev Microbiol. 2018. Link

Best-practice review for microbiome study design, molecular technology choice, data analysis and multi-omics integration. The authors recommend exact sequence variants (ASVs) over OTU-based analyses; discuss methods for combining metagenomic and metabolomic data; and address compositional data analysis, where progress has been particularly rapid. Classical concerns of experimental design and research reproducibility remain critical. Keeping these in mind allows deeper insight from microbiome datasets across human and environmental contexts.

[542] McDonald D, Hyde E, Debelius JW et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018. Link

The American Gut Project compared >10 000 citizen-scientist stool samples from the US, UK and Australia with environmental samples using Earth Microbiome Project standardized protocols. Human stool microbiomes showed unexpectedly wide beta-diversity compared with environmental samples. Open data integration enabled discovery of new molecules and untargeted-metabolomic associations with diverse plant intake (a stronger predictor than reductive categorical variables like veganism). The work demonstrates feasibility of mail-shipped, self-collected microbiome samples for reproducing known and revealing new associations, including psychiatric illness links and individual perturbations such as surgery.

[543] Allaband C, McDonald D, Vázquez-Baeza Y et al. Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians. Clin Gastroenterol Hepatol. 2019. Link

Clinically-oriented review of microbiome content, intersubject and intrasubject variability, study-design considerations and confounders, and laboratory and computational methods for reading microbiota, gene products and metabolites. Common pitfalls for clinicians are highlighted: the misconception that an individual's microbiome is stable; that diet induces rapid changes large relative to interindividual differences; that all people share a core stool microbiome; and that all lab/computational pipelines yield equivalent results. Understanding current limits and future promise is essential for translation to routine clinical care.

[545] Walsham NE, Sherwood RA. Fecal calprotectin in inflammatory bowel disease. Clin Exp Gastroenterol. 2016. Link

IBD and IBS share many clinical symptoms, so accurate diagnosis is essential since IBD therapy is evolving rapidly while IBS is largely managed symptomatically. Clinical assessment combined with imaging and endoscopy has long been the diagnostic mainstay. Over the past decade fecal biomarkers of GI inflammation — chiefly calprotectin, a neutrophil cytosolic protein — have entered routine use. Calprotectin enables objective assessment of disease activity and treatment response in the chronic remitting-relapsing IBD courses (Crohn's disease, ulcerative colitis).

[546] Scheffler L, Crane A, Heyne H et al. Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family. Front Endocrinol. 2018. Link

The authors show that the widely used commercial zonulin ELISA does not measure pre-haptoglobin-2 ('true' zonulin): mass spectrometry identified complement C3 and properdin (complement factor P) as the proteins recognized by the kit, not pre-HP2 — undermining the validity of zonulin data obtained with this assay as a barrier marker.

[547] Rezaie A, Buresi M, Lembo A et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: The North American Consensus. Am J Gastroenterol. 2017. Link

Pre-meeting survey questions across five domains (indications, preparation, performance, interpretation, knowledge gaps) were sent to 17 clinician-scientists; 10 attended a live meeting. Using an evidence-based approach, 28 statements were finalized and anonymously voted by the working group. Consensus was reached on 26 statements covering all five domains. These guidelines aim to standardize indications, methodology and interpretation of breath tests for carbohydrate maldigestion syndromes and small intestinal bacterial overgrowth (SIBO).

[548] Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS. Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations. Trends Microbiol. 2019. Link

Next-generation sequencing in microbiome research enables high-sensitivity community surveys but also efficiently detects contaminant DNA and cross-contamination, especially in low-biomass samples. The authors review sources and impacts of contamination and identify key measures to mitigate it. They propose a minimum-criteria checklist, 'RIDE', to improve the validity of future low-microbial-biomass studies — covering reagent and instrument controls, internal contamination tracking, DNA dilution series and experimental positive controls.

[549] Karstens L, Asquith M, Davin S et al. Controlling for Contaminants in Low-Biomass 16S rRNA Gene Sequencing Experiments. mSystems. 2019. Link

Same dataset as ref-471: a mock community dilution series tested four computational decontamination methods (negative-control filtering, abundance filtering, Decontam, SourceTracker). Contaminant DNA proportion rose with decreasing biomass — 80,1% in the most diluted sample. The benchmark guides choice of bioinformatic contamination-removal pipelines, particularly for low-microbial-biomass samples where in silico methods have inherent limits.

[558] Kennedy KM, de Goffau MC, Perez-Muñoz ME et al. Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies. Nature. 2023. Link

The authors evaluate recent studies claiming microbial colonization of human fetuses and the intrauterine environment from reproductive-biology, microbial-ecology, bioinformatic, immunological, clinical-microbiological and gnotobiological perspectives. They conclude that detected microbial signals are likely the result of contamination during sampling, DNA extraction or sequencing. The existence of live, replicating microbial populations in healthy fetal tissue is incompatible with established immunological, clinical-microbiological and germ-free-mammal-derivation principles. The fetal microbiome serves as a cautionary example of low-biomass-sequencing pitfalls and the need for a trans-disciplinary approach.

[559] Drossman DA, Hasler WL. Rome IV — Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016. Link

Drossman and Hasler's 2016 Gastroenterology paper introduces Rome IV — the major revision of the Rome diagnostic criteria for Functional GI Disorders, now reframed as 'Disorders of Gut-Brain Interaction'. The new framework integrates biopsychosocial, microbiota-gut-brain-axis, and visceral hypersensitivity concepts, replacing the older 'functional' label with a mechanism-aware terminology. The paper outlines updates to the diagnostic criteria for IBS, functional dyspepsia, functional constipation/diarrhoea, abdominal pain, and other disorders, with revised symptom frequency thresholds and subtype definitions. Rome IV is the operative reference for functional GI/DGBI diagnosis worldwide, cited extensively in clinical practice, research and microbiome-IBS literature.

[560] Thomas RL, Jiang L, Adams JS et al. Vitamin D Metabolites and the Gut Microbiome in Older Men. Nat Commun. 2020. Link

Cross-sectional analysis of 567 older men: higher active 1,25(OH)2D levels were associated with greater abundance of butyrate-producing bacteria (including Faecalibacterium) and higher microbial diversity. Causal direction is undetermined, but the positive association is supported in human data.

[561] Hill C, Guarner F, Reid G et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014. Link

An ISAPP expert panel convened in October 2013 reviewed the probiotic field 13 years after the original FAO/WHO definition. The panel affirmed the FAO/WHO definition — 'live microorganisms which when administered in adequate amounts confer a health benefit on the host' — as still relevant and sufficiently broad to accommodate current and anticipated applications. Inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified in light of advances in science and use. The consensus statement promotes more precise use of the term 'probiotic' to help clinicians and consumers differentiate products on the market.

[562] Su GL, Ko CW, Bercik P et al. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020. Link

Su, Ko, Bercik and colleagues' 2020 Gastroenterology paper presents the American Gastroenterological Association (AGA) Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. The expert panel reviewed evidence across pouchitis, Clostridioides difficile infection, antibiotic-associated diarrhoea, IBS, IBD, acute infectious gastroenteritis (adults and children), and necrotising enterocolitis. The guideline conditionally recommends probiotics for selected indications (pouchitis prophylaxis: VSL#3; necrotising enterocolitis prevention: combination Lactobacillus + Bifidobacterium products), and recommends against probiotics for IBS, IBD induction/maintenance and acute infectious gastroenteritis in adults due to insufficient evidence. The guideline is the operative AGA reference for evidence-based probiotic use in GI disorders.

[563] Gibson GR, Hutkins R, Sanders ME et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017. Link

An ISAPP expert panel convened in December 2016 reviewed and updated the definition of prebiotics. Consistent with the original concept, the updated definition states that a prebiotic is 'a substrate that is selectively utilized by host microorganisms conferring a health benefit'. The expanded definition allows for non-carbohydrate substrates, applications beyond the gastrointestinal tract, and use in diverse non-food categories; the requirement for selective microbiota-mediated mechanisms is retained. Documented beneficial health effects are required, and the definition applies to both human and animal prebiotics.

[564] Salminen S, Collado MC, Endo A et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021. Link

An ISAPP panel in 2019 reviewed the increasingly used but inconsistently defined term 'postbiotic'. They defined a postbiotic as 'a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host'. Effective postbiotics must contain inactivated microbial cells or cell components, with or without metabolites, contributing to the observed health benefit. The panel discussed existing evidence for postbiotic health effects, proposed mechanisms of action, required levels of evidence, safety considerations and stakeholder implications.

[565] Wilson BC, Vatanen T, Cutfield WS, O'Sullivan JM. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol. 2019. Link

FMT is highly effective for recurrent Clostridium difficile infection but its efficacy in chronic dysbiosis-associated diseases has been modest and variable. Multiple studies suggest FMT outcome depends on stool donor microbial diversity and composition, leading to the concept of FMT 'super-donors'. The review explores keystone species as predictors of FMT success and discusses how host genetics and diet may influence engraftment and maintenance — providing a framework for more targeted, donor-stratified bacteriotherapy.

[588] Ahmed S, Spence JD. Mediterranean diet, the gut microbiome and meditation: a systematic review. Nutrients. 2022. Link

Diet and physical activity both shape the gut microbiota with health-relevant consequences. The review summarizes current knowledge of how Western, ketogenic, vegan, gluten-free and Mediterranean diets, as well as intensive, endurance and aerobic exercise modalities, modify microbiota composition and function. Numerous factors — sex, age, lifestyle, drug therapies — also influence the microbiota, linking it to disease and immune disorders. Diet–microbiota and exercise–microbiota interactions emerge as actionable levers for prevention and management of cardiovascular, neuroendocrine, respiratory and musculoskeletal disease.

[592] Mutlu EA, Comba IY, Cho T et al. Inhalational exposure to particulate matter air pollution alters the composition of the gut microbiome. Environ Pollut. 2018. Link

C57BL/6 mice were exposed to concentrated ambient particulate matter (PM) or filtered air for 8 h/day, 5 days/week for 3 weeks via inhalation. After exposure GI tract tissues and feces were collected and the gut microbiota analyzed. The model addresses how PM — directly deposited or indirectly delivered via mucociliary clearance and saliva/mucus swallowing — alters GI epithelium and microbiota. Findings link inhaled air pollution to gut microbiota changes, supporting an airway–gut axis as a mechanism by which ambient PM may contribute to gastrointestinal disease.

[593] Duan H, Yu L, Tian F et al. Gut microbiota: A target for heavy metal toxicity and a probiotic protective strategy. Sci Total Environ. 2020. Link

Heavy metal (HM) exposure may contribute to metabolic-disease progression via gut-microbiota perturbation. The review describes the bidirectional relationship: HMs alter gut microbiota composition and function, while gut bacteria affect HM uptake and metabolism through physical-barrier effects, pH and oxidative-balance modulation, and altered expression of detoxification enzymes and metal transporters. Gut microbiota also influence intestinal barrier integrity, indirectly affecting HM absorption. Probiotic strategies — enhancing intestinal HM sequestration, detoxifying HMs, modulating metal-transporter expression and maintaining barrier function — are reviewed as protective approaches against HM-induced dysbiosis.

[599] Bokulich NA, Chung J, Battaglia T et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016. Link

Microbial development was profiled in 43 US infants over the first two years of life. Early-life exposures — antibiotic use, cesarean section and formula feeding — were associated with disrupted establishment of maternal bacteria, delayed microbiome development and altered α-diversity. These findings illustrate the complexity of early-life microbiome maturation and its sensitivity to common perturbations during the critical neonatal window — relevant to long-term immune and metabolic risk.

[600] Imhann F, Bonder MJ, Vich Vila A et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016. Link

PPI use and gut microbiota composition were assessed by 16S sequencing in 1815 individuals across three cohorts. PPI users vs non-users were compared per cohort and meta-analyzed. PPIs are among the top 10 most-used drugs worldwide and have been associated with enteric infection risk, particularly Clostridium difficile. The study confirms that PPI use alters gut microbiome composition in directions that may impair colonization resistance — providing mechanistic underpinning for the epidemiological association between PPIs and enteric infection.

[601] Targownik LE, Fisher DA, Saini SD. AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Gastroenterology. 2022. Link

A clinical update provides Best Practice Advice statements for PPI de-prescribing in ambulatory patients. PPIs are among the most-prescribed medications and are increasingly used for indications with uncertain benefit, contributing to polypharmacy and economic burden. PPI use has been increasingly associated with PPI-associated adverse events (PAAEs). The guidance promotes structured de-prescribing strategies to reduce pill burden, real costs and theoretical risks while ensuring patients with appropriate indications continue therapy.

[605] Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe. 2011. Link

Why only some carcinogen-exposed or genetically predisposed individuals develop cancer is unexplained. Beyond classical factors, the human microbiome — bacteria, archaea, eukaryotes and viruses colonizing humans from birth — has emerged as a modulator. The review presents principles and paradigms of microbiome-related malignancy through three case studies: microbiota effects on local and adjacent neoplasia, the 'estrobolome' model of distant hormonal effects on hormone-dependent cancers, and complex interactions between the microbiome and a latent virus leading to malignancy.

[609] Berg G, Rybakova D, Fischer D et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome. 2020. Link

An international expert panel within the EU MicrobiomeSupport project (approx. 40 leaders, supported by over 100 online survey respondents) addressed the lack of a commonly agreed definition of the term 'microbiome'. The paper proposes a definition based on the compact, comprehensive description provided by Whipps et al. in 1988, supplemented by new recommendations reflecting the latest technological and research developments. A consensus on best practices and a clearer conceptual framework are intended to harmonize microbiome research across disciplines.

[610] Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016. Link

Reported values for cell counts in the body vary by orders of magnitude and are rarely supported by measurements. Integrating up-to-date information, the authors estimate the total bacterial count in a 70 kg 'reference man' at 3,8·10^13. They estimate 3,0·10^13 human cells, with the hematopoietic lineage dominating the count (about 90%). The widely cited 10:1 bacteria-to-human-cell ratio is revised: bacterial and human cell numbers are of the same order, with a total bacterial mass of about 0,2 kg.

[612] Earle KA, Billings G, Sigal M et al. Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe. 2015. Link

The authors present BacSpace, a flexible software package, plus an imaging pipeline for high-throughput quantification of intestinal microbiota spatial organization within immunofluorescence images of fixed gut cross-sections. Applied to gnotobiotic and human microbiota-colonized mice, the pipeline showed that eliminating microbiota-accessible carbohydrates (MACs) thins distal-colon mucus, increases microbial proximity to the epithelium, and elevates the inflammatory marker REG3β. A MAC-deficient diet also alters monophyletic spatial clustering. The approach generalizes to other contexts (Helicobacter pylori invasion of mouse gastric glands), enabling spatial-functional studies of host-microbiota interaction.

[613] Smith PM, Howitt MR, Panikov N et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013. Link

The authors investigated regulation of Foxp3+ colonic regulatory T cells (Tregs), which control intestinal inflammation. Short-chain fatty acids (SCFAs) produced by gut microbiota regulated the size and function of the colonic Treg pool and protected against colitis in an Ffar2-dependent manner in mice. The findings establish a class of abundant microbial metabolites as a mechanism of microbiota-immune coadaptation, supporting colonic homeostasis and providing a molecular rationale for SCFA-based interventions in inflammatory bowel disease.

[615] Atarashi K, Tanoue T, Oshima K et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013. Link

Starting from a healthy human fecal sample, a sequential selection strategy isolated 17 bacterial strains from the indigenous human microbiota that strongly induce CD4+FOXP3+ regulatory T (Treg) cells and anti-inflammatory mediators (IL-10, ICOS) in colonized germ-free mice. Genome sequencing showed all 17 strains fell within Clostridia clusters IV, XIVa and XVIII, which lack prominent toxins and virulence factors. The work provides a rational, defined-consortium approach to developing immune-modulating probiotics for allergic and inflammatory disease.

[617] Lindell AE, Zimmermann-Kogadeeva M, Patil KR. Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota. Nat Rev Microbiol. 2022. Link

The review summarizes mechanisms of interactions between gut bacteria and xenobiotics — antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. Beyond diet, small-molecule drugs and other xenobiotics have emerged as major effectors of gut microbiota composition and function, with consequences for drug metabolism, immunomodulation and disease risk. Understanding these bidirectional interactions is essential for personalized medicine and for assessing environmental exposures.

[619] Mishra A, Lai GC, Yao LJ et al. Microbial exposure during early human development primes fetal immune cells. Cell. 2021. Link

Fetal immune-priming was explored by profiling microbial signals across fetal organs using 16S rRNA sequencing. Low but consistent microbial signals were detected in fetal gut, skin, placenta and lungs during the 2nd trimester. Several live bacteria — including Staphylococcus and Lactobacillus — were isolated and induced in vitro activation of memory T cells in fetal mesenteric lymph node. SEM and RNA-ISH visualized bacteria-like structures and eubacterial RNA within the 14-week fetal gut lumen, supporting selective live-microbe presence and a role in pre-birth immune priming. (Interpretation is contested — see ref-558 and ref-479.)

[623] Stewart CJ, Ajami NJ, O'Brien JL et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018. Link

TEDDY-study longitudinal stool samples (3–46 months of age) from 903 children — 12 005 16S rRNA and 10 867 metagenomic samples — defined three developmental phases of the gut microbiome: developmental (months 3–14), transitional (months 15–30) and stable (months 31–46). Receipt of breast milk (exclusive or partial) was the most significant factor influencing microbiome structure; breastfeeding was associated with higher Bifidobacterium species (B. breve, B. bifidum), and cessation of breastfeeding accelerated Firmicutes-marked maturation. The findings characterize microbial-immune cross-talk relevant to islet autoimmunity and type 1 diabetes development.

[624] von Hertzen L, Hanski I, Haahtela T. Natural immunity. Biodiversity loss and inflammatory diseases are two global megatrends that might be related. EMBO Rep. 2011. Link

Von Hertzen, Hanski and Haahtela's 2011 EMBO Reports commentary 'Natural immunity. Biodiversity loss and inflammatory diseases are two global megatrends that might be related' synthesises an ecological-immunological perspective linking declining environmental biodiversity to the rising burden of inflammatory and allergic disease. The authors propose that reduced contact with diverse environmental microbes — driven by urbanisation, antiseptic environments, processed food and loss of biodiverse landscapes — impairs immune tolerance training in early life, contributing to allergy, asthma, IBD and autoimmune disease. They link the hygiene/'old friends' hypothesis to global biodiversity-loss data and call for environmental health policy integrating microbiome exposure as a public-health intervention. The article is a foundational reference for the biodiversity-microbiome-health framework.

[625] Fitzstevens JL, Smith KC, Hagadorn JI et al. Systematic review of the human milk microbiota. Nutr Clin Pract. 2017. Link

A systematic review of PubMed (Jan 1964 – June 2015) characterized the microbiota of human milk. Twelve studies met the inclusion criteria (healthy mothers, English-language, identifying bacteria in human milk by culture-independent methods, reporting results at genus level). Studies varied in geography and in milk collection, storage and analytic methods. Human-milk microbes appear to colonize the infant gut early and may influence short- and long-term infant health outcomes; methodological heterogeneity limits cross-study comparison and underscores the need for standardized protocols.

[626] Biagi E, Nylund L, Candela M et al. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010. Link

Gut microbiota of young adults, elderly and centenarians (>100 years) were profiled by HITChip and qPCR of 16S rRNA. Young adults and 70-year-olds had highly similar microbiota; centenarians differed significantly. After 100 years of symbiosis, the microbiota showed Firmicutes rearrangement and enrichment of facultative anaerobes including pathobionts. The compromised microbiota was associated with 'inflammageing' — elevated inflammatory markers in peripheral blood — partly explained by marked decrease of anti-inflammatory Faecalibacterium prausnitzii and relatives in centenarians.

[628] Rothschild D, Weissbrod O, Barkan E et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018. Link

Genotype and microbiome data from 1046 healthy individuals across multiple ancestries demonstrated that gut microbiome composition is not significantly associated with genetic ancestry, and host genetics play only a minor role. Conversely, genetically unrelated household-sharing individuals had significantly similar microbiomes. Over 20% of inter-person microbiome variability was associated with diet, drugs and anthropometric measurements. Microbiome data significantly improved prediction accuracy for several human traits (glucose, obesity metrics) compared with models using only host genetics and environment. Microbiome-targeted interventions may translate across diverse genetic backgrounds.

[629] Kurilshikov A, Medina-Gomez C, Bacigalupe R et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021. Link

The MiBioGen consortium analyzed genome-wide genotypes and 16S fecal microbiome data from 18 340 individuals across 24 cohorts. Microbial composition varied widely between cohorts (only 9 of 410 genera detected in >95% of samples). A genome-wide association study identified 31 loci affecting microbiome composition at p<5×10^-8. One locus — the lactase (LCT) gene — reached study-wide significance (p=1,28×10^-20) and showed age-dependent association with Bifidobacterium abundance. Additional suggestive associations were enriched for high-heritability taxa and intestinal/brain-expressed genes. Mendelian randomization implicated microbiome causality in ulcerative colitis and rheumatoid arthritis.

[630] Cortese R, Lu L, Yu Y et al. Epigenome-Microbiome crosstalk: a potential new paradigm influencing neonatal susceptibility to disease. Epigenetics. 2016. Link

Crosstalk between the immature gut's epigenome and initial bacterial colonization was investigated at critical neonatal stages, relevant to necrotizing enterocolitis (NEC) in preterm infants. Exposing immature enterocytes to probiotic and pathogenic bacteria produced over 200 regions of differential DNA modification, with exposure-specific patterns. Reciprocally, a mouse model of prenatal dexamethasone exposure showed that antenatal glucocorticoids alter the host's epigenome. Findings support a model in which microbe-driven epigenetic programming establishes neonatal inflammatory and barrier properties, predisposing to NEC.

[631] Asnicar F, Berry SE, Valdes AM et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat Med. 2021. Link

Deep metagenomic sequencing of 1203 gut microbiomes from 1098 PREDICT-1 individuals (with detailed long-term diet and hundreds of fasting/postprandial cardiometabolic markers) revealed strong associations of microbes with specific nutrients, foods and dietary indices, driven especially by healthy plant-based foods. Microbial obesity biomarkers were reproducible in external cohorts and aligned with circulating cardiovascular blood metabolites. Some microbes (Prevotella copri, Blastocystis spp.) predicted favorable postprandial glucose; overall composition predicted multiple cardiometabolic blood markers. Healthy-diet microbes overlapped with markers of favorable postprandial metabolism, providing a scalable resource for stratifying microbiomes by health level.

[632] Berry SE, Valdes AM, Drew DA et al. Human postprandial responses to food and potential for precision nutrition. Nat Med. 2020. Link

PREDICT-1 enrolled n=1002 twins and unrelated UK adults to assess postprandial metabolic responses in clinic and at home. Identical meals produced large inter-individual variability in postprandial triglyceride (CV 103%), glucose (68%) and insulin (59%) responses. Person-specific factors such as gut microbiome contributed 7,1% of variance to postprandial lipemia versus 3,6% from meal macronutrients; for postprandial glycemia, macronutrients contributed more (15,4% vs 6,0% microbiome). Genetic variants had modest effect (9,5% glucose, 0,8% triglyceride, 0,2% C-peptide). A US cohort (n=100) independently validated the findings; a machine-learning model predicted triglyceride (r=0,47) and glycemic (r=0,77) responses to food.

[634] Schmitt FCF, Brenner T, Uhle F et al. Gut microbiome patterns correlate with higher postoperative complication rates after pancreatic surgery. BMC Microbiol. 2019. Link

Prospective clinical pilot study in 32 patients undergoing pancreatic surgery: 116 stool samples were analyzed by 16S rRNA next-generation sequencing. One preoperative baseline sample (without surgical stress/antibiotics) and at least two postoperative samples within 10 days were obtained per patient, with additional samples taken upon postoperative complications. The study aimed to characterize gut-microbiome changes after pancreatic surgery and correlate them with the postoperative course, exploring the microbiome's role in postoperative complications — including barrier dysfunction and bacterial translocation.

[636] Barton W, Penney NC, Cronin O et al. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level. Gut. 2018. Link

Metabolic phenotyping and functional metagenomic analysis compared professional international rugby-union players (n=40) and controls (n=46), correlating results with lifestyle (e.g. diet) and clinical measurements (e.g. serum creatine kinase). Athletes had relative increases in metagenomic pathways (amino-acid and antibiotic biosynthesis, carbohydrate metabolism) and fecal metabolites (acetate, propionate, butyrate) associated with enhanced muscle turnover and health. Differences between athletes and sedentary controls were greater at the metagenomic and metabolomic levels than at the compositional level, providing added insight into the diet-exercise-gut-microbiota paradigm.

[638] Chaix A, Manoogian ENC, Melkani GC, Panda S. Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases. Annu Rev Nutr. 2019. Link

Molecular clocks are present in almost every cell to anticipate daily recurring and predictable changes, such as rhythmic nutrient availability, and to adapt cellular functions accordingly. At the same time, nutrient-sensing pathways can respond to acute nutrient imbalance and modulate and orient metabolism so cells can adapt optimally to a declining or increasing availability of nutrients. Organismal circadian rhythms are coordinated by behavioral rhythms such as activity-rest and feeding-fasting cycles to temporally orchestrate a sequence of physiological processes to optimize metabolism. Basic research in circadian rhythms has largely focused on the functioning of the self-sustaining molecular circadian oscillator, while research in nutrition science has yielded insights into physiological responses to caloric deprivation or to specific macronutrients. Integration of these two fields into actionable new concepts in the timing of food intake has led to the emerging practice of time-restricted eating. In this paradigm, daily caloric intake is restricted to a consistent window of 8-12 h.

[640] Park BJ, Tsunetsugu Y, Kasetani T et al. The physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field experiments in 24 forests across Japan. Environ Health Prev Med. 2010. Link

This paper reviews previous research on the physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing), and presents new results from field experiments conducted in 24 forests across Japan. The term Shinrin-yoku was coined by the Japanese Ministry of Agriculture, Forestry, and Fisheries in 1982, and can be defined as making contact with and taking in the atmosphere of the forest. In order to clarify the physiological effects of Shinrin-yoku, we conducted field experiments in 24 forests across Japan. In each experiment, 12 subjects (280 total; ages 21.7 +/- 1.5 year) walked in and viewed a forest or city area. On the first day, six subjects were sent to a forest area, and the others to a city area. On the second day, each group was sent to the other area as a cross-check.

[2614] Chassaing B, Compher C, Bonhomme B et al. Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Gastroenterology. 2022. Link

16-subject controlled-feeding RCT in human volunteers. Diet containing carboxymethylcellulose (CMC, E466) emulsifier altered gut microbiota composition within 11 days, decreased microbial diversity and fermentation metabolite levels, and two participants showed signs of bacterial encroachment into the mucus layer. First human evidence that CMC at approved daily exposure levels has detrimental microbiological effects.

[2615] Sutton EF, Beyl R, Early KS et al. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metabolism. 2018. Link

Cross-over RCT with 8 men with prediabetes: restricting meals to an early 6-hour window (eTRF, 8:00–14:00) for 5 weeks — under energy-matching — significantly improved insulin sensitivity, β-cell response, blood pressure, and oxidative stress compared to a 12-hour control window. Weight loss was NOT required for these favourable metabolic changes, indicating the effect arises from circadian alignment.

[2616] Wilkinson MJ, Manoogian ENC, Zadourian A et al. Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome. Cell Metabolism. 2020. Link

12-week single-arm trial with 19 patients with metabolic syndrome: a daily 10-hour eating window (TRE) — without other dietary or activity changes — significantly reduced body weight, waist circumference, blood pressure, LDL cholesterol, and HbA1c. The magnitude of improvements is clinically meaningful, the intervention was well tolerated and voluntarily continued post-study. Confirms TRE as a safe and effective adjunct in metabolic syndrome management.

[2617] {EFSA Panel on Dietetic Products Nutrition,, Allergies (NDA). Scientific Opinion on Dietary Reference Values for carbohydrates and dietary fibre. EFSA Journal. 2010. Link

Scientific opinion of EFSA's NDA Panel on dietary reference values for carbohydrates and dietary fibre. Recommends 25 g/day fibre intake for adequate bowel function and 25–30 g/day for reduced metabolic and cardiovascular risk in adults. European reference value underpinning national guidelines (DGE, NHS, MDOSZ).

[2619] McGill CR, Fulgoni VL, Devareddy L. Ten-Year Trends in Fiber and Whole Grain Intakes and Food Sources for the United States Population: National Health and Nutrition Examination Survey 2001-2010. Nutrients. 2015. Link

Ten-year trend analysis of dietary fiber and whole grain intakes from NHANES 2001–2010 (n≈30,000). Mean fiber intake in the US adult population was 16–18 g/day across the entire study period — substantially below the recommended 25–38 g/day. High fiber intake correlated with whole grains, vegetables, fruits, legumes, and nuts. Classic reference for US fiber intake gap.

[2620] Alderete TL, Jones RB, Chen Z et al. Exposure to traffic-related air pollution and the composition of the gut microbiota in overweight and obese adolescents. Environmental Research. 2018. Link

Cohort of 43 overweight and obese Latino adolescents examined the relationship between air pollution (PM2.5 and NO₂) and gut microbiota composition. Participants living in higher-pollution neighborhoods showed reduced microbial diversity and elevated dominance of the Coriobacteriaceae family, which was also correlated with insulin resistance. One of the first human studies documenting the relationship between ambient PM levels and gut microbiota.

[2713] Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. The Lancet. 1984. Link

Marshall and Warren's 1984 Lancet paper identified the curved bacterium later named Helicobacter pylori on the gastric mucosa of patients with gastritis and gastric/duodenal ulceration, reinforced by Marshall's famous self-experiment. It rewrote ulcer pathology, replacing the prior "stress and acid" paradigm with an infectious model and enabling antibiotic eradication therapy. The work received the 2005 Nobel Prize in Medicine.

[2714] Alang N, Kelly CR. Weight Gain After Fecal Microbiota Transplantation. Open Forum Infectious Diseases. 2015. Link

Case report of a previously normal-weight woman, successfully treated with FMT for recurrent Clostridioides difficile infection, who became obese over 16 months (BMI 26→33) after receiving stool from an overweight (related) donor. The case raised the possibility that a donor's metabolic phenotype is partly transferable to the recipient via the microbiota. A single case is not causal proof (other factors may have contributed), but it underscores the importance of donor selection and screening.

[2715] Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Journal of Biological Chemistry. 1992. Link

Eng and colleagues isolated the peptide exendin-4 from the venom of the Gila monster (Heloderma suspectum). It is structurally similar to the human incretin hormone GLP-1 but resists rapid degradation by DPP-4, giving it a much longer duration of action. This serendipitous discovery became the foundation of the GLP-1 receptor agonist drug class: a synthetic version of exendin-4 (exenatide) became the first approved GLP-1 agonist in 2005, paving the way for today's semaglutide and tirzepatide.

[2716] Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021. Link

The STEP 1 phase-3, randomized, placebo-controlled trial (n=1961 adults with overweight/obesity, without diabetes) compared once-weekly subcutaneous semaglutide 2.4 mg with placebo plus lifestyle counselling over 68 weeks. The semaglutide group achieved a mean weight reduction of ~14.9% versus ~2.4% with placebo. The most common adverse events were gastrointestinal (nausea, diarrhea), mostly transient.

[2717] (experimental study, high-fat diet-induced obese mice). Effects of semaglutide on metabolism and gut microbiota in high-fat diet-induced obese mice. Frontiers in Pharmacology. 2025. Link

Animal (high-fat diet-induced obese mouse) study indicating that semaglutide favorably modifies serum metabolism and gut microbiota composition, with part of the metabolic improvement transferable via fecal transplantation. IMPORTANT: this is preclinical, animal-model evidence; human relevance is not yet established, so the claim should be treated as a hypothesis ().

[2718] Tomás-Barberán FA, García-Villalba R, González-Sarrías A, Selma MV, Espín JC. Urolithin metabotypes from ellagitannin-rich foods and association with cardiometabolic risk. Molecular Nutrition & Food Research. 2017. Link

From the ellagitannins in pomegranate and walnuts, the gut microbiota produces urolithins; individuals fall into three metabotypes by which urolithins they can produce (UM-A, UM-B, and non-producer UM-0). The producing profile is determined by microbiota composition and correlates with cardiometabolic risk markers — meaning the same food can have different health effects across individuals. A key example of the "microbial by-product" (postbiotic) concept and personalized nutrition.

[2719] Setchell KDR, Clerici C. Equol: history, chemistry, and formation. The Journal of Nutrition. 2010. Link

Review of equol, a metabolite formed by gut bacteria from soy's daidzein isoflavone. Only about 25–30% of the population are "equol producers" — i.e., harbor the appropriate gut bacteria — which may explain why studies of soy's health effects are contradictory. Equol-producer status is a microbiota-dependent metabotype and an early, well-documented example of personalized nutrition.

[2720] Zeevi D, Korem T, Zmora N, et al. Personalized Nutrition by Prediction of Glycemic Responses. Cell. 2015. Link

In an 800-person cohort, nearly 47,000 post-meal glucose responses were measured with continuous glucose monitoring. Individuals' responses to the same food varied substantially, partly predicted by gut microbiota composition. The authors built a machine-learning personalized model that outperformed nutrient-based calculation, and a short personalized dietary intervention reduced glucose excursions. A cornerstone of the "no one-size-fits-all" nutrition paradigm.

E.2 Further reading for lay readers

The reading suggestions below are for readers who want to place the picture this book outlines into context — these are narrative and popular-science works, not journal articles. The selection criterion is scientific reliability: this list excludes titles that substitute marketing-level promises for clinical evidence. Easily available editions in print or e-book format.

Popular-science books

• Spector T. The Diet Myth. 2015 — still one of the best lay overviews
• Knight R. Follow Your Gut. 2015 (TED Books)
• Sonnenburg J, Sonnenburg E. The Good Gut. 2015
• Enders G. Gut: The Inside Story of Our Body's Most Underrated Organ. 2015

Trustworthy websites

• ISAPP (International Scientific Association for Probiotics and Prebiotics): isappscience.org
• American Gut Project: humanfoodproject.com/americangut
• WGO (World Gastroenterology Organisation) Global Guidelines: worldgastroenterology.org

Podcasts

• Stanford Center for Continuing Medical Education podcasts
• American Gastroenterological Association podcasts

E.3 Further reading for clinicians

Recommendations for clinical readers: systematic reviews, clinical guidelines, and professional consensus documents that present microbiome medicine at clinically relevant depth. The selection focuses on 2022–2025 publications (excluding already classic milestone works). All entries include PubMed/DOI access.

Recent systematic reviews

• Annual microbiome overviews in Nat Rev Gastroenterol Hepatol
• Lancet Gastroenterology & Hepatology

Key journals

• Gut (BMJ)
• Gastroenterology (AGA)
• Cell Host & Microbe
• Microbiome (BMC)
• Nature Reviews Gastroenterology & Hepatology

Conferences and societies

• ISAPP annual meetings
• DDW (Digestive Disease Week)
• UEG Week (United European Gastroenterology Week)
• National gastroenterology societies
• Regional microbiome consortia

Consensus documents as framework

• ISAPP probiotic, prebiotic, postbiotic consensus papers ([@ref-561, @ref-563, @ref-564])
• ESCMID, ECCO IBD guidelines
• Rome IV criteria for functional bowel disorders