The gut microbiome and dysbiosis

You get to know the invisible ecosystem living in your bowel: what the microbiome is, why diversity matters, and what dysbiosis means — the loss of balance that is the real breeding ground for the return of C. difficile.

What is the microbiome?

In your bowel you are not alone: several trillion bacteria, fungi and other tiny living beings live there in a continuously working, coordinated community. This living community is collectively called the microbiome^[G] — and the entirety of the bacteria living in it is called the microbiota^[G]. Though invisible, this community is one of our most important "organs": it carries out numerous tasks that our own body is not capable of on its own.

These beneficial inhabitants, for example, help digest the fibres that your body could not break down on its own, and meanwhile they produce valuable substances that nourish the bowel wall. They train your immune system to recognise what is friend and what is foe. And — as you saw in the previous chapters — they occupy the space and the nutrients from pathogens, maintaining the protective colonisation resistance^[G].

The secret of how it works is diversity. A healthy gut microbiome contains several hundred different bacterial species, each carrying out a different task. This richness is what makes the community stable and resistant: if there are many kinds of inhabitants, the system can balance out smaller disturbances. The poorer and more one-sided the flora, the more fragile it is.

When the balance is upset: dysbiosis

Dysbiosis^[G] means the state in which this delicate balance is upset: diversity decreases, some of the beneficial inhabitants disappear, and ground is gained by those that under normal conditions would stay in the background. The flourishing, diverse city becomes poor, deserted streets, where there is no longer anything to protect order.

From the point of view of C. difficile infection, dysbiosis is the key concept. As the guiding idea of the book also states: C. difficile is not a simple infection but the consequence of dysbiosis. When the flora thins out — most often because of antibiotics — C. difficile can multiply precisely in this emptied-out space. And as long as the dysbiosis persists, the infection can return again and again, however much we fight it with repeated antibiotic courses.

This is why durable recovery cannot be achieved purely by overcoming the pathogen — the dysbiosis itself must be reversed. There are two ways to restore the diverse flora: on the one hand, to replace the missing beneficial community directly (this is what DiffBiome FMT^[G] does, which the next chapter is about), and on the other, to create the conditions under which this community can flourish — many kinds of fibre-rich food, good sleep, less stress. The coming weeks of the programme build up exactly this in you.

Diversity as a goal

One of the recurring messages of the programme is diversity. It is not just about "eating healthily" — but about consuming as many kinds of plant sources as possible, because every type of fibre gives food to a different beneficial bacterium. A one-sided diet fattens up a few inhabitants while starving many; a varied diet containing many plants nourishes the whole community, and with it strengthens diversity, that is, protection.

Right now, during the course, this is not yet your main task — your bowel is still healing, and the gentle, easily digestible diet is what is appropriate. But it is worth being aware of the goal already: over the coming weeks, gradually, with small daily steps, we build up the varied diet and lifestyle that keep your flora diverse and resistant over the long term.

🍽️ Eating during these days

During these three days you get to know what the microbiome and dysbiosis are — and that for durable recovery the diverse flora must be rebuilt. Eating still follows the gentle line for now: plenty of fluids, easily digestible but not one-sided foods, with soluble fibre. On days 13 and 14, pair every meal with something gentle and plant-based, and pay attention to the flora's "environment" too — enough sleep, less stress — because these help engraftment just as much as food does.

From day 15 a new stage begins: from this day on, the Plant Calendar recommends one specific plant source for each day, along the gentle, firming line. The plant of day 15 is the green banana, which is rich in resistant starch: this type of starch "resists" digestion in the small intestine, reaches the large intestine intact, and there nourishes the good bacteria while supporting a firmer stool. A ripe but still slightly firm banana is a perfect start at this point — and from here on, a new gentle source will come for each day.

References

[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.

[160] Chassaing B, Van de Wiele T, De Bodt J, Marzorati M, Gewirtz AT. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut. 2017. Link

Using the M-SHIME ex vivo human microbiota model that excludes host inflammation as a confounder, both carboxymethylcellulose (CMC) and polysorbate 80 (P80) acted directly on the human microbiota to increase its pro-inflammatory potential, evidenced by elevated bioactive flagellin. The CMC-induced flagellin rise was rapid (1 day) and driven by altered microbial gene expression. The findings establish that these dietary emulsifiers exert direct, host-independent pro-inflammatory effects on the human gut microbiota.

[339] Suez J, Zmora N, Zilberman-Schapira G et al. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018. Link

In a controlled study of post-antibiotic microbiome reconstitution, multi-strain probiotic supplementation, autologous fecal microbiota transplantation (aFMT) or spontaneous recovery were compared in mice and humans, sampled via invasive mucosal biopsies. Antibiotics enhanced probiotic mucosal colonization in humans but only mildly in mice. Compared with spontaneous recovery, probiotics induced a markedly delayed and persistently incomplete reconstitution of indigenous stool and mucosal microbiota and host transcriptome, while aFMT produced rapid, near-complete recovery within days. In vitro, Lactobacillus-secreted soluble factors contributed to probiotic-mediated suppression of indigenous taxa. The findings caution against routine post-antibiotic probiotic use and support aFMT as a recovery strategy.

[365] Reed AD, Theriot CM. Contribution of Inhibitory Metabolites and Competition for Nutrients to Colonization Resistance against Clostridioides difficile by Commensal Clostridium. Microorganisms. 2021. Link

This review examines how commensal Clostridium species mediate colonization resistance against C. difficile. Commensal Clostridia modify primary bile acids into secondary bile acids that suppress C. difficile spore germination and vegetative outgrowth. They additionally produce antimicrobial peptides and short-chain fatty acids that directly inhibit C. difficile and compete for limiting nutrients such as proline, important for C. difficile growth via Stickland fermentation. Loss of commensal Clostridia after broad-spectrum antibiotics is a key mechanistic step toward CDI susceptibility. The authors argue that restoring defined Clostridium consortia is a rational, mechanism-driven alternative to FMT for preventing recurrent CDI.

[369] Weingarden A, González A, Vázquez-Baeza Y, Weiss S, Humphry G, Berg-Lyons D, Knights D, Unno T, Bobr A, Kang J, Khoruts A, Knight R, Sadowsky MJ. Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection. Microbiome. 2015. Link

This study tracked fecal microbiota dynamics in four patients with multiply recurrent, antibiotic-refractory C. difficile infection treated with FMT, sampling daily up to 28 days and weekly up to 84 days post-FMT (with sampling out to 151 days). 16S rRNA gene profiling was compared to Human Microbiome Project body-site references. Pre-FMT samples were markedly dysbiotic. FMT produced a rapid normalization of fecal community composition toward a healthy donor-like state within days, and this normalization was largely sustained over months. Time-course visualization highlighted both rapid early shifts and longer-term stabilization. The findings document the kinetics of FMT-driven microbiota recovery in refractory CDI and support its durability.