Antibiotics and colonisation resistance

You understand why it is precisely the antibiotic that opens the door to C. difficile: it empties out the protective flora that had kept the pathogen in check. This protection is called colonisation resistance.

The invisible protective shield — colonisation resistance

Picture your bowel as a crowded, well-functioning city, where every spot is taken and every resource has an owner. The many kinds of beneficial bacteria^[G] occupy the surface of the bowel wall, use up the available nutrients, and produce substances that make the environment unfavourable for intruders. A newly arriving pathogen — C. difficile, for example — simply has nowhere to settle and nothing to multiply from.

This natural protection is called colonisation resistance^[G]. It is not a drug, not a treatment — simply one of the most important "side effects" of a healthy, diverse gut flora^[G]. As long as this shield is intact, C. difficile spores may even be present in the bowel and still cause no harm: they have no room to germinate and multiply.

Colonisation resistance is therefore not the merit of a single bacterium but of variety, of diversity. The more kinds of beneficial inhabitants your bowel has, the more stable and resistant the protection. This explains why a varied, fibre-rich diet is so important in the later weeks of the book: it nourishes this protective community and makes it diverse.

What happens when you take an antibiotic?

The antibiotic is an indispensable medicine that saves lives in many infections — this is not about it being bad. The problem is that most antibiotics cannot be selective: while they destroy the bacterium they were prescribed for, they also thin out or destroy a large part of the gut flora's beneficial inhabitants. Part of the crowded, well-protected city suddenly empties out.

In this emptied-out, thinned-out flora, colonisation resistance collapses: space and food are freed up. If C. difficile spores are present at this point, they get a free hand — they germinate, multiply, and begin to produce the toxins that cause the complaints. This is the typical scenario: someone receives an antibiotic for an infection, and then a few days or weeks later develops C. difficile-caused diarrhoea.

This is why the DiffBiome course emphasises so strongly that the flora must be restored, not merely the pathogen overcome. And this is why it is an essential rule that if you are still taking an antibiotic, it must be finished before starting the course — otherwise the antibiotic would also destroy the freshly delivered beneficial bacteria. The details of taking the capsules are covered in a later chapter, but it is good to keep this rule in mind already.

While you were waiting: the cautious antibiotic policy during the course

During and after the course it is particularly worth handling antibiotics consciously. This does not mean that you may never take an antibiotic again — there are situations where it is unavoidable and right. But every unnecessary, not strictly justified antibiotic course is a risk: it can again thin out the flora that is now rebuilding, and open the door to relapse.

That is why, if in the coming weeks and months you should need an antibiotic for another reason, always mention to the doctor that you have had a C. difficile infection and are on a DiffBiome course. That way they can weigh up whether the antibiotic is truly necessary, and if so, can choose one that damages the gut flora less. Prevention and antibiotic policy are discussed in detail in a later phase of the programme.

🍽️ Eating during these days

During these three days you understand how the antibiotic empties out the protective flora — and your eating now serves to let your bowel settle while this protection rebuilds. Since the danger of diarrhoea and dehydration still remains, the goal is a gentle, firming diet: plenty of fluids, easily digestible foods and soluble fibre. Soluble fibre forms a gel in water, which slows the passage of bowel contents and supports a firmer stool, while plenty of fluids replace the amount lost with the looser stool. Your concrete tasks: on all three days take the daily dose according to the usual routine, drink an extra glass of water after every looser stool, and do not start a further antibiotic or probiotic course on your own that would once again disturb the flora that is now rebuilding.

In this early phase there is not yet a daily plant — the Plant Calendar only starts from day 15. For now stay with easily digestible, boiled or steamed foods, and avoid raw, coarse, strongly gas-forming foods; the gradual building-up of a varied, fibre-rich diet comes later, as the symptoms settle.

References

[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.

[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.