Reviewing Evidence from Clinical Trials for the Role of the Gut Microbiome in Disease
Many lines of evidence strongly suggest that alterations to the gut microbiome are an important contributing factor in the onset and progression of many different conditions, including age-related conditions. Comparatively few clinical trials touch on this relationship, however, despite the recent approval of a fecal microbiota transplant intervention for the treatment of Clostridioides difficile infection. That will change with time, but for now there is sufficiently little clinical trial data that a short paper can summarize it all.
Composed of an elaborate ecosystem of bacteria, fungi, viruses, and protozoa residing in the human digestive tract, the gut microbiome influences metabolism, immune modulation, bile acid homeostasis, and host defence. Through observational and preclinical data, the gut microbiome has been implicated in the pathogenesis of a spectrum of chronic diseases ranging from psychiatric to gastrointestinal in nature. Until recently, the lack of unequivocal evidence supporting a causal link between gut microbiome and human health outcomes incited controversy regarding its significance. However, recent randomised controlled trial (RCT) evidence in conditions, such as Clostridioides difficile infection, cancer immunotherapy, and ulcerative colitis, has supported a causal relationship and has underscored the potential of the microbiome as a therapeutic target.
This review delineates the RCT evidence substantiating the potential for a causal relationship between the gut microbiome and human health outcomes, the seminal observational evidence that preceded these RCTs and the remaining knowledge gaps. The association between the gut microbiome and human health has long been supported by multiple lines of observational evidence including in vitro, in vivo, and epidemiologic data. Recent RCTs of microbiome therapeutics have bridged the gap between association and causation and have definitively demonstrated that microbiome-altering therapeutics can improve human health outcomes in CDI. Further, smaller RCTs in UC and cancer immunotherapy, but not obesity, suggest the probable benefit of microbiome therapeutics across other indications as well.
It appears that more than a few Findings on the gut microbiome and inflamaging are discussed in the Human Cell Atlas - quantifying the nearly 6,000 cell types of our 37-10^12 cells; often with investigations comparing different ages and racial backgrounds -- hopefully a useable version of it will be available in the next year or 2. Not a substitute for clinical data of course.
"Future directions" outlined by the authors don´t seem to realistically lead to any applicability in the foreseeable future. Different approach(es) needed. Academic theory and (responsible) evidence based practice in life science: more often than not unbridgeable gaps. Theory of (life) science should change. Nir Barzilai (e.g.) a few years ago has been bold enough to make a proposal, but e.g. questionable academic career requirements depending on publishing papers necessitating ever more (theoretical) papers (how often l´art pour l´art ?) with no actionable implementation results retard real life science application progress irresponsibly. Life science/medicine is based on (responsible) trial and error. That should be re-instated.