Transplanting Microbes for Irritable Bowels or Irritated Microbes or Both?

See “Fecal microbiota transplantation reduces symptoms in some patients with irritable bowel syndrome predominant abdominal bloating: short- and long-term results from a placebo-controlled randomized trial,” by Holvoet T, Joossens M, Vázquez-Castellanos JF, et al, on page 145. Fallacies still flourish medicine when language corrupts logic. Unexplained conditions, such as (IBS), are often referred to “functional” because of the apparent absence physical findings. This invokes an outdated false dichotomy, “dysfunctional” might be more accurate descriptor.1Quigley E.M. Shanahan F. The medicine: words servants scoundrels.Clin Med (Lond). 2009; 9: 131-135Crossref PubMed Scopus (12) Google Scholar Moreover, there findings many IBS. Visceral hypersensitivity is objective finding evident at colonoscopy, albeit awkward quantify. However, bloating underappreciated, diagnostically valuable that distresses patients, quantifiable simple tape measure. How clinicians bother record it precisely? Therefore, noteworthy al2Holvoet T. M. J.F. al.Effects fecal syndrome: trial.Gastroenterology. 2021; 160 (145–157)Google report this issue Gastroenterology, were selected for their randomized, placebo-controlled, clinical trial microbial (FMT) authors’ rationale selection was based evidence suggesting those flatulence most likely have disturbances gut microbiota. notion may contestable, not same flatulence, nor exclusively due “a build-up gas.”3Malagelada J.R. Accarino A. Azpiroz Bloating distension: old misconceptions current knowledge.Am J Gastroenterol. 2017; 112: 1221-1231Crossref (40) Scholar,4Barba E. Sánchez B. Burri al.Abdominal distension after eating lettuce: role intestinal gas evaluated vitro CT imaging.Neurogastroenterol Motil. 2019; 31e13703Crossref (4) Regardless, will welcome bloating, which notoriously difficult manage. FMT associated symptom relief about one-half compared one-quarter receiving placebo (autologous stool). result particularly impressive given refractory IBS included, refractoriness being identified prior failure respond ≥3 conventional therapies Importantly, investigators able provide beneficial effects probably transplanted microbes process itself had no influence microbiome. Thus, baseline microbiome did differ post-treatment sample group autologous Responders tended higher diversity before treatment, but specific taxa or enterotype predictive good outcome. Unfortunately, cure, benefit persisted only median 4 months diminished over 1 year. longitudinal follow-up provided useful information. responders nonresponders discrete stable subsets initial responders, whom effect lost time, again retransplanted. In contrast, remained disappointing failed initially retreated stool different donor. Does suggest way forward stratifying IBS? Symptoms are, course, central diagnosis questionable value condition. Experienced know so-called constipation, diarrhea, mixed, alternating patterns undergo transitions one another time.5Drossman D.A. Morris C.B. Hu Y. al.A prospective assessment habit women: defining alternator.Gastroenterology. 2005; 128: 580-589Abstract Full Text PDF (166) Patients frequently insist they can >1 pattern day! Furthermore, few ever confirm presence constipation both measured. Close listening essential inadequacies express patient’s heightened sense incomplete evacuation, misinterpreted “constipation” “diarrhea” imprecise history taking.6Shanahan illness. Liberties Press, Dublin2020Google studies support stratification diarrhea.7Jeffery I.B. Das O'Herlihy al.Differences microbiomes metabolomes people vs without bile acid malabsorption.Gastroenterology. 2020; 158: 1016-1028.e8Abstract (61) It seems reasonable incorporate analysis design monitoring future trials therapy IBS, especially microbiome-based therapies. does imply disturbed respond, predict differential responsiveness improved patient data interpret results. There been previous inconsistent results, differences study design, subsets, routes transplant delivery confound meaningful comparisons. several caveats consider regarding al.2Holvoet Excluded who account one-third psychiatric comorbidity substantial proportion practice also excluded. statistically significant preponderance males limb (59%) active treatment (31%), unusual bothersome showed marked gender difference response FMT, females responding significantly better than males. addition, use nasojejunal preceded macrogol prep quite distinct process, immunologically physiologically, commonly used colonoscopic delivery. Although major adverse attributable occurred relatively small population studied trials, threshold toxicity should always low non–life-threatening conditions incongruent enthusiasts cite murine experiments implicating pathogenesis ignore similar possibility transferable phenotypes. risks limited infection transmission antibiotic-resistant organisms; include theoretical transfer inflammatory, metabolic, even behavioral phenotypes donor recipient.8Walter J. Armet A.M. Finlay B.B. al.Establishing exaggerating causality microbiome: lessons human microbiota-associated rodents.Cell. 180: 221-232Abstract (173) Donor minimize these risks, microbiotas seem represent hidden risk development colon cancer.9Flemer Lynch D.B. Brown J.M. al.Tumour-associated non-tumour-associated colorectal cancer.Gut. 66: 633-643Crossref (350) Scholar, 10Dai Z. Coker O.O. Nakatsu G. al.Multi-cohort cancer metagenome altered bacteria across populations universal bacterial markers.Microbiome. 2018; 6: 70Crossref (169) 11Wirbel Pyl P.T. Kartal al.Meta-Analysis metagenomes reveals global signatures cancer.Nat Med. 25: 679-689Crossref (333) inform components increase (or decrease) one’s cancer? Microbial informative experiment, curiously its mechanism action any condition incompletely understood. due, part, normal has defined,12Shanahan Ghosh T.S. O’Toole P.W. What definition healthy microbiome?.Gastroenterology. (in press)Abstract (52) multiple coincidental actions, direct host, restoration missing network interactions,7Jeffery modulation administered including phage (Figure 1). Microbiome-based evolve scientifically defined microbes, offer Fecal Microbiota Transplantation Reduces Some With Irritable Bowel Syndrome Predominant Abdominal Bloating: Short- Long-term Results From Placebo-Controlled Randomized TrialGastroenterologyVol. 160Issue 1PreviewIrritable (IBS) functional gastrointestinal disorder dysbiosis. Given reported promising open-label we efficacy trial. Full-Text