Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features

Abstract

Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.

Contrasting Strategies: Human Eukaryotic Versus Bacterial Microbiome Research

“…However, gut colonization of bacterial probiotics is not uniform in humans, and mice seem not to be colonized at all (Zmora et al. ). This is also the case for eukaryote probiotics.…”

With Probiotics, Resistance Is Not Always Futile

“…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).…”

“…The companion paper (investigating empiric probiotics without antibiotics) by Zmora et al (2018) demonstrates that the baseline microbiota composition in the stool quickly returns to near-normal after cessation of probiotics for most patients, with a sub-population of individuals being persistently colonized with bacteria found in the probiotics. Furthermore, host steady-state mRNA levels from gut biopsies suggest there is a different signature in individuals who are persistently colonized by probiotic strains compared to those who return more quickly to their baseline microbiome.…”

“…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.…”