Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT

Abstract

Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution and host transcriptome recovery toward homeostatic configuration, while aFMT induced a rapid and near-complete recovery within days of administration. In vitro, Lactobacillus-secreted soluble factors contributed to probiotics-induced microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits may be offset by a compromised gut mucosal recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection without compromising microbiome recolonization in the antibiotics-perturbed host.

The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases

“…One key area is extending the successes seen in the various mouse models to the so far more limited successes seen in clinical trials, as already reported for the use of probiotics in intestinal diseases (Suez et al, 2018). In spite of this, there is still much more that needs to be done.…”

With Probiotics, Resistance Is Not Always Futile

“…Furthermore, it is critical that we discern the underlying mechanisms of bacterio-therapy and the personalization that may be required to determine which populations would benefit most from this therapy. Suez et al (2018) show that there is a delay in returning the microbiome to its pre-antibiotic state after probiotics when compared to watchful waiting and that an auto-FMT induces the most rapid and complete recovery in previously healthy subjects (this is also recapitulated in a mouse model). Several key questions arise from these data, including whether there is an inherent resistance to repopulation by the probiotic species (and if so, what causes this resistance), or if there are specific patient populations that are more likely to benefit from bacteriotherapy.…”

“…Moving clinical microbiome research from a correlative to mechanistic science is an ongoing challenge. Work by Suez et al (2018) and Zmora et al (2018) in the September 6 th issue of Cell takes us one step closer to understanding how the gut microbiota and the host respond to probiotics alone or after dysbiosis from antibiotics with the addition of probiotics or auto-FMT (fecal transplant from the same individual at a later time).…”

“…Fundamentally, Suez et al (2018) and Zmora et al (2018) demonstrate a convincing, statistically significant difference in how bacteriotherapy may restore the microbiome after dysbiosis in a healthy human population, but whether these data have broader health implications in individuals who are unwell remains unknown. Populations that may be most likely to benefit from bacterio-therapy are those who are unwell: for example, those with prolonged anti-biotic-associated diarrhea or individuals who are immunocompromised and thus at risk to acquire opportunistic infections.…”

“…The work by Suez et al (2018) and Zmora et al (2018) helps to unravel the mechanisms of colonization and persistence of and host responses to probiotics and FMT, strengthening the possibility of future ‘‘personalized microbiome’’ bacteriotherapies. Looking forward, research focused on microbial interactions—both within the microbiota and between the microbiota and host—should include careful analysis of the relevant biogeography of microbial colonization as well as host responses.…”