III. Phase 2 – Engraftment and lifestyle (days 25–60)

III. 11 What to avoid: antibiotics, PPIs, ultra-processed foods

Sometimes the most important thing is what we DON'T do. Unnecessary antibiotics, needless acid suppressants and ultra-processed foods all undermine the freshly engrafted gut flora. This chapter teaches you to recognise and avoid the three main traps.

Summary

In healing, what you leave out matters at least as much as what you build in. Behind recurrent C. difficile[G] infection there is almost always a breakdown of the gut flora[G], and three everyday factors are especially capable of sustaining this breakdown or triggering it anew: unnecessary antibiotics, needlessly taken acid suppressants (PPIs), and a lot of ultra-processed food. None is a "sin" in itself – antibiotics and acid suppressants really are sometimes needed – but for all three it is worth knowing when they help and when they harm, so that you don't undermine the freshly engrafted flora. In this chapter you will learn to recognise the three main traps and get concrete, everyday rules with which to steer clear of them – always working together with your treating physician, because you should never alter your medications on your own.

Antibiotics – the biggest risk

Antibiotics are the most important trigger of C. difficile infection. The logic is simple: an antibiotic does not discriminate, it destroys the disease-causing and the beneficial bacteria at the same time. When the protective gut flora is thinned out, C. difficile gets free room to overgrow. It was precisely this process that created your original infection, and it is precisely this that can trigger a relapse too – especially now, when the transplanted flora is still only taking root.

This does not mean you may never take antibiotics again. There will be situations – a severe bacterial infection – when they really are necessary. The goal is that you don't receive antibiotics needlessly: for a viral cold or flu, for example, they are of no use, because those are not bacteria. If any doctor wants to prescribe an antibiotic, always mention that you have been through C. difficile infection and are on an FMT course – this is important information that can influence the decision and the type of agent chosen.

As for the DiffBiome course: if you do need an antibiotic for some reason, the basic rule is that the antibiotic must be finished at least 48 hours before starting DiffBiome, otherwise the antibiotic would destroy the freshly delivered flora too. Always coordinate this with your treating physician.

The acid suppressant (PPI) – the silent risk

The proton pump inhibitor – PPI for short – is the most common acid-suppressing medication (they often end in "-prazole": omeprazole, pantoprazole and the like). Many people take them for heartburn or reflux, sometimes for years, without reconsidering whether they are still really needed.

Why does this matter for C. difficile? Stomach acid is one of your body's natural lines of defence: it destroys most of the swallowed pathogens before they reach the gut. If you persistently suppress acid production, this line of defence weakens, and unwanted bacteria can settle more easily – research has linked long-term PPI use with a higher C. difficile risk.

The important message: never stop this medication on your own, because some people genuinely need it (for example with ulcers or severe reflux). But it is worth discussing with your treating physician: is taking it still really justified, could the dose perhaps be reduced, or could it be replaced with lifestyle steps? It often turns out that an acid suppressant started long ago is no longer needed.

Ultra-processed foods – the everyday risk

The third trap lies in eating. Ultra-processed foods[G] are those heavily industrially transformed products that contain many additives, emulsifiers[G], refined sugar and little fibre – think of packaged sweets, sugary soft drinks, fast food, the many brightly packaged snacks. These give exactly the opposite of what your engrafting gut flora needs.

Your gut flora, you see, lives on fibre and varied plant matter. Ultra-processed foods, by contrast, are low in fibre and, in return, full of additives (certain emulsifiers, for example) that, according to research, can disturb the protective layer of the gut lining and the balance of the flora. If these dominate your diet, the beneficial bacteria starve, while substances that burden the flora reach the gut in abundance.

You don't have to strive for perfection, and you don't have to change everything at once. The goal is to shift the balance: the more natural, minimally processed food on your plate – vegetables, fruit, legumes, whole grains, and, where your symptoms allow, gradually more fibre – and the less packaged, ultra-processed product. (Building the diet in detail is covered in a separate chapter; here the point is avoidance.) If your gut is sensitive, introduce fermenting, high-fibre foods step by step, watching your symptoms – in some cases a temporary, gentler (FODMAP[G]-aware) approach can also help; discuss this with your treating physician.

Oral hygiene – the often-forgotten connection

Few of us would think that our mouth has anything to do with our gut flora – yet the oral cavity is the body's first microbiome station, and what happens there matters further down too. The bacteria living in the mouth continuously reach the gut by being swallowed; if the oral flora breaks down (e.g. untreated gum inflammation, periodontal disease), persistent, inflammation-promoting bacteria can pass from it into the gut, and this can burden the balance of the gut flora too. The good news is that this is exactly the kind of area you can keep in hand with simple daily habits.

The point is not complicated: regular, twice-daily toothbrushing, cleaning between the teeth (floss or interdental brush), and – something many people skip – gently cleaning the tongue, because plaque and bacteria settle on the back of the tongue too. It is also worth keeping up regular dental check-ups, because untreated gum and periodontal disease is a quietly persisting source of inflammation.

One caution: use strong, antiseptic (bacteria-killing) mouthwashes only in moderation, and not as a persistent daily routine, unless your dentist specifically recommends it. These too do not discriminate – they kill off the beneficial bacteria of the mouth as well – so their persistent, unjustified use can actually reduce the diversity[G] of the oral flora. The daily basis is mechanical cleaning (brush, floss); mouthwash is at most a supplement.

Medication review – go through what you take, with your doctor

Beyond the PPI, it is worth going through your long-term medications with your doctor from time to time. Many people have for years been taking agents that were started for an old complaint, and since then no one has questioned whether they are still needed. The period after CDI is a good occasion for just such a "medication stocktake".

Pay particular attention to two groups. One is the acid suppressant (PPI), discussed above. The other is unnecessary or repeated antibiotics: if you frequently get antibiotics on a "just to be safe" basis, each time this thins out your protective gut flora again. Besides these, agents that slow gut motility or dry out the mouth and gut (some antispasmodics, anticholinergic medications) can also affect the flora and the symptoms.

The rule here is the same as with the PPI: never stop or change a medication on your own. Your task is to list what you take and ask the question, "is each one still justified?" – the weighing-up and the decision are your treating physician's. Often it is precisely such a review that reveals that something is no longer needed, or that there is a gentler alternative for the gut.

🩺 Clinical block

Antibiotic exposure is the strongest modifiable risk factor for CDI: disruption of the colonisation resistance of the normal microbiota (reduced diversity, disturbance of bile-acid metabolism, a shift in the primary/secondary bile-acid ratio) allows the germination and vegetative overgrowth of C. difficile spores (Reed and Theriot 2021 [003]). After antibiotic-induced perturbation, the microbiota recovers only partially and slowly (Dethlefsen and Relman 2011 [033]), which keeps the recurrence[G] window persistently open. The datasheet protocol: the antibiotic must be finished ≥48 hours before DiffBiome; probiotic supplementation is also to be avoided during the course.

Proton pump inhibitors, by raising gastric pH, impair the gastric bactericidal barrier and modify the composition of the upper-GI microbiota (decreased diversity, increased C. difficile abundance; Imhann et al. 2016 [012]); a systematic review and meta-analysis associated gastric acid suppression with an increased risk of recurrent CDI (Tariq et al. 2017 [154]). Deprescribing is a clinician's decision and is warranted when the indication no longer applies; the withdrawal may proceed either by gradual dose reduction or by abrupt discontinuation – the guideline regards both as acceptable – but the patient must be informed that transient upper-GI symptoms may occur on withdrawal because of rebound acid hypersecretion (Targownik et al. 2022 [085]). Among dietary factors, dietary emulsifiers (e.g. carboxymethylcellulose, polysorbate-80) can, according to animal and human data, thin the mucus layer and induce pro-inflammatory dysbiosis (Chassaing and colleagues 2015 [036], 2017 [037]). An ultra-processed, low-fibre diet worsens colonocyte energy supply by withdrawing substrate from SCFA-producing taxa (Hamer et al. 2008 [062]); under fibre deprivation – in a gnotobiotic mouse model – the microbiota begins to degrade the glycoproteins of the intestinal mucus and erodes the mucosal barrier (Desai et al. 2016 [068]). Hence, during the engraftment phase, UPF reduction and gradual fibre introduction are a reasonable support; the link between fibre intake and strain engraftment is also supported by a randomised human trial (Gogokhia 2025 [454]).

The oral–intestinal axis is clinically relevant: the oral cavity is the second-largest microbial reservoir, and oral pathobionts (e.g. Porphyromonas gingivalis, Fusobacterium nucleatum, oral Klebsiella/Enterobacteriaceae strains) translocate by swallowing into the lower GI tract, where they can settle ectopically in a dysbiotic, dysmotile or pro-inflammatory milieu; periodontal disease is associated with systemic inflammation and altered gut-microbiota composition (after Atarashi and colleagues 2017 [077]). Oral hygiene (mechanical plaque control, periodontal treatment) is thus a complementary element of CDI prevention, through reducing the oral pathogen load. Broad-spectrum antiseptic mouthwashes (e.g. persistent chlorhexidine use) suppress the oral nitrate-reducing commensals (Kapil et al. 2013 [078]), so their persistent use without indication is to be avoided – mechanical plaque control is primary. Medication review (PPI deprescribing, antibiotic stewardship, review of anticholinergic/motility-inhibiting burden) is a clinician's decision.

Day 55 – Antibiotic awareness

Today you fix your "protective rules" regarding antibiotics. The goal is that, in any medical situation, you know what to say.

  • Prepare a short sentence to tell every doctor: "I have been through C. difficile infection, I am on an FMT course";
  • Be aware: antibiotics do not work on a viral cold/flu;
  • If an antibiotic were needed, coordinate: it must be finished ≥48 hours before DiffBiome;
  • Diary: medications, how you feel, a note.
Day 56 – Reviewing the medication list

Today, with your treating physician, you review what you take – with special attention to the acid suppressant. Don't change anything on your own.

  • List all the medications and supplements you take regularly;
  • Check whether you are taking a PPI (often ending in "-prazole"); if so, discuss with your doctor whether it is still justified;
  • Medication review: besides the PPI, also ask about repeated antibiotics and motility-slowing/anticholinergic agents – "is each one still justified?" (the decision is the doctor's);
  • Also mark on the list the probiotic paused during the course;
  • Diary: medications, stool count, Bristol, how you feel.
Day 57 – The pantry screen

Today you focus on eating: you review how much ultra-processed food there is, and you start shifting the balance. Not a ban, but swaps.

  • Review what is at home: mark the ultra-processed products (packaged sweets, sugary soft drinks, salty snacks);
  • Swap at least one such product for a natural alternative (e.g. water instead of soft drink, fruit instead of crisps);
  • Introduce fibre and fermenting foods gradually, watching your symptoms;
  • Oral hygiene reminder: twice-daily toothbrushing + interdental cleaning + tongue cleaning; use strong antiseptic mouthwash only in moderation – the oral flora is part of your gut flora too;
  • Diary: content of meals, bloating, stool count, Bristol.

🍽️ Eating during these days

The theme of these three days is what is worth avoiding, and one of its pillars is precisely eating: the concrete task of day 57 is to review how much ultra-processed food there is in your home and to start shifting the balance – swap at least one such product for a natural alternative (water instead of soft drink, fruit instead of crisps), and introduce fibre and fermenting foods gradually, watching your symptoms. The other two days (antibiotic awareness – day 55; reviewing the medication list – day 56) support eating indirectly: the fewer the substances burdening the flora, the better a nourishing diet is put to use.

For these days, the Plant Calendar (Appendix F) recommends steamed broccoli (day 55), steamed cauliflower (day 56) and kale (day 57) – three cruciferous vegetables, steamed, gently prepared. These days fall into the calendar's "diversity / fermentable fibres" (days 51–70) phase, where the aim is the active building of microbiome diversity. The fermentable fibre of cruciferous vegetables is the substrate of the fibre-degrading bacteria, from which short-chain fatty acids[G], including butyrate[G], are formed and nourish the gut lining – exactly the opposite of what a low-fibre, ultra-processed diet gives. These natural, minimally processed plants are thus practical examples of the balance-shift this chapter is about; with a sensitive gut, introduce them too gradually, steamed, watching your symptoms.

📊 Data

During the "avoidance" phase, record daily:

  • medications taken (especially antibiotics, PPIs) and a note;
  • time/content of meals and an estimate of the ultra-processed proportion;
  • bloating (0–5);
  • daily stool count and Bristol scale – core CDI data;
  • bloody stool (yes/no) – core CDI data;
  • DiffBiome dose (capsules/day) and LOT number;
  • Movement: type + minutes, step count (target/actual);
  • Stress level (1–5) and mood (1–5);
  • Sleep (hours + quality 1–5).
⚠️ Never alter your medications on your own

This chapter is about awareness, not about stopping medications on your own. Antibiotics, the PPI and any other regular medication may be altered or stopped only in consultation with your treating physician – suddenly stopping a necessary medication carries serious risk. Your task is to pass on the information (that you have been through CDI and are on FMT) and to ask the question; the decision is the doctor's.

Why does this matter?

The three main everyday triggers of relapse – unnecessary antibiotics, a needless PPI and an ultra-processed diet – all sustain or re-trigger the breakdown of the gut flora, exactly when your new flora should be taking root. Avoiding them is largely a matter of awareness and a few everyday rules – always working together with your doctor.

References

[003] 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 conclude from this that new therapies against CDI are urgently needed; the clinical validation of defined *Clostridium* consortia comes not from this review but from the VE303 phase 2 trial [56].

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

Imhann and colleagues' 2016 Gut paper reports that proton pump inhibitor (PPI) use significantly alters the human gut microbiota. Combining three population cohorts (>1800 individuals) with 16S rRNA sequencing, the authors show that PPI users have decreased microbial diversity and consistent shifts in 20% of bacterial taxa: increases in oral-cavity bacteria (Streptococcaceae, Enterococcaceae), Enterobacteriaceae and *Clostridium* difficile, alongside decreases in commensals such as Ruminococcaceae and Bifidobacteriaceae. These shifts mechanistically explain epidemiological associations between PPI use and CDI, enteric infection, hepatic encephalopathy and SIBO. The work supports prudent PPI prescribing and deprescription efforts.

[033] Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences of the United States of America. 2011. Link

Stanford-based longitudinal study tracking the gut microbiota of three individuals over 10 months across two consecutive courses of ciprofloxacin, with deep 16S rRNA sequencing. Loss of bacterial diversity was profound and rapid, occurring within 3-4 days of antibiotic initiation, and recovery toward the pre-treatment state was often incomplete months after cessation. Repeated antibiotic exposure produced incremental, non-recoverable shifts in community composition. With over 2,000 citations, this paper is the canonical reference establishing that antibiotic-induced dysbiosis is not a self-correcting disturbance but can leave a lasting ecological imprint – central to the case for MTT in patients with cumulative antibiotic exposure history.

[036] Chassaing B, Koren O, Goodrich JK, Poole AC, Srinivasan S, Ley RE, Gewirtz AT. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015. Link

Landmark Nature paper showing that two ubiquitous dietary emulsifiers – carboxymethylcellulose (CMC, E466) and polysorbate-80 (P80, E433) – induced low-grade intestinal inflammation even at relatively low concentrations, altered microbiota composition, and produced obesity/metabolic syndrome in wild-type mice. The authors themselves note that the extent of human emulsifier consumption is not tracked, but that, given how widespread emulsifiers are in food production, actual human exposure may exceed the 1.0 percent level used in the experiment. In mice predisposed to colitis, the same compounds triggered overt colonic inflammation. The authors propose emulsifier exposure as a contributor to the post-1950 rise in IBD and metabolic disease. A corrigendum has been issued for the paper (Corrigendum: *Nature* 2016;536(7615):238). This is the central evidence cited in Section 8.3 of this Guide regarding industrial food production as a chronic input into dysbiosis.

[037] 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

Follow-up to Chassaing 2015 extending the findings from mice to a human-microbiota model (the M-SHIME ex vivo system). Both emulsifiers increased the pro-inflammatory potential of the microbiota, demonstrably so through elevated flagellin levels; the composition of the community, however, was altered only by P80, while the effect of CMC operated through microbiota gene expression. The rise in lipopolysaccharide levels occurred only with P80, and at higher doses. When a suspension of the emulsifier-treated microbiota was administered to immunodeficient (RAG−/−) mice, serum IL-6 levels rose significantly. The work confirms that the murine findings translate to human gut ecology and reinforces the argument that dietary reform is a clinical, not an aesthetic, component of the maintenance phase.

[062] Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. The role of butyrate on colonic function. Aliment Pharmacol Ther. 2008. Link

Narrative review summarizing the bioactivity of butyrate — a SCFA produced by colonic microbial fermentation of dietary fibre — and its mechanisms in human colonic function. Butyrate is the primary energy source for colonocytes and modulates inflammation, carcinogenesis, mucosal barrier integrity, oxidative stress, permeability, and satiety. The review consolidates evidence on butyrate as a central effector of colonic homeostasis and a target for dietary interventions in colonic disease.

[068] 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.

[077] Atarashi K, Suda W, Luo C et al. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science. 2017. Link

This gnotobiotic study showed that salivary Klebsiella strains, when colonizing the gut, are strong inducers of T helper 1 (TH1) cells. These antibiotic-resistant Klebsiella strains colonize when intestinal microbiota are dysbiotic and elicit severe gut inflammation in genetically susceptible hosts. The findings establish the oral cavity as a reservoir for potential intestinal pathobionts that exacerbate disease such as IBD when ectopically colonizing the gut.

[078] Kapil V, Haydar SM, Pearl V, Lundberg JO, Weitzberg E, Ahluwalia A. Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med. 2013. Link

This randomized crossover study in 19 healthy volunteers tested whether suppressing oral nitrate-reducing bacteria with chlorhexidine antiseptic mouthwash affects systemic nitrite levels and blood pressure. Blood pressure (clinic, home, 24-hour ambulatory) was measured during a 7-day control period and a 7-day chlorhexidine treatment period. Mouthwash use suppressed oral nitrate-reducing flora, reduced systemic nitrite and significantly increased blood pressure. The findings demonstrate that oral microbiota actively contribute to systemic blood pressure regulation via the enterosalivary nitrate-nitrite-NO pathway.

[085] 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.

[154] Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis. JAMA Intern Med. 2017. Link

Systematic review and meta-analysis of whether gastric acid suppression (mainly PPIs, and H2 blockers) is associated with the risk of **recurrent** *Clostridioides difficile* infection. Five databases were searched from 1995–2015; case-control, cohort and clinical studies were included in which CDI patients did or did not receive gastric acid suppression and recurrence was assessed. Gastric acid suppression was associated with significantly higher odds of recurrent CDI (pooled OR about 1.5). This entry is the source for the III.11 claim that long-term PPI use carries an elevated risk of recurrent CDI. **LIMITATION:** a meta-analysis of observational studies — association, not causation; the authors themselves caution about residual confounding (PPI users are often sicker/older), so unsupervised discontinuation is not warranted, only clinical review.

[454] Gogokhia L, Tran N, Grier A, Nagayama M, Xiang G, Funez-dePagnier G, Lavergne A, Ericsson C, Ben Maamar S, Zhang M, Battat R, Scherl E, Lukin DJ, Longman RS. Donor composition and fiber promote strain engraftment in a randomized controlled trial of fecal microbiota transplant for ulcerative colitis. Med. 2025. Link

The MINDFUL randomized, double-blind, placebo-controlled trial assigned 27 patients with mild-to-moderate ulcerative colitis to a single FMT or placebo, with or without psyllium fibre supplementation, over 8 weeks. FMT induced clinical response, remission and endoscopic improvement versus placebo (p < 0.05). Fibre supplementation did not improve clinical outcomes, but strain-level metagenomic analysis showed that donor community composition together with recipient fibre intake shaped donor-strain engraftment. This is among the first randomized human evidence that post-procedure dietary (exposome) factors directly influence FMT engraftment, while showing that improved engraftment does not automatically translate into better clinical outcomes. ClinicalTrials.gov: NCT03998488.

Authors:
PG
Dr. Patay Gábor
physician, microbiota specialist
BA
Dr. Bezzegh Attila
medical director, clinical microbiologist
AM
Dra. Anna Munar
physician, exposome specialist
MicroBiome Bank — medically reviewed professional content. Last updated: 2026.