Gut mucosal microbiome in probiotic and antibiotic intervention

Abstract (1):Empiric probiotics are commonly consumed in 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 a person-, region- and microbial-specific mucosal colonization patterns, hallmarked by differential baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, highly-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.Abstract (2):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 recovery, probiotics induced a markedly delayed and persistently-incomplete indigenous stool/mucosal microbiome reconstitution and gut transcriptome recovery to steady-state 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 microbiome and host recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection, without compromising microbiome recolonization in the antibiotics-perturbed host.

Classified as human gut / stool shotgun DNA metagenome of adult by deterministic_prior with confidence 0.90. Assay shotgun_dna.

• host external_curation.infant_catalog · “infant triage reason_code age_adult_only”
• body site study.title · “host features resist gut mucosal colonization by”
• body site study.description · “evidence of probiotic gut mucosal colonization efficacy”
• life stage external_curation.infant_catalog · “infant triage reason_code age_adult_only”

1,613 runs over 1,613 samples · mean 1.28 Gbp per run (median 1.18 Gbp, total 2,058.10 Gbp; 1,613 runs with a base count) · layout PAIRED 1,613 · platform ILLUMINA 1,613 · models NextSeq 500 (1,613) · 84% of runs with a Sandpiper profile · first public 2018-09-14

Lind AL first · Pollard KS last · Montassier E first · Valdés-Mas R · Batard E · Zmora N · Dori-Bachash M · Suez J · Elinav E last · Dubinsky V first · Dotan I · Gophna U last · Eriksen C first · Moll JM · Myers PN · Pinto ARA · Danneskiold-Samsøe NB · Dehli RI · Rosholm LB · Dalgaard MD · Penders J · Jonkers DM · Pan-Hammarström Q · Hammarström L · Kristiansen K · Brix S last · Frolova MS first · Kiselev SS · Panyukov VV · Ozoline ON last

PRJEB28097.csv.gz (36.5 KB) · parquet (122.3 KB) — all 1,613 samples, every field with route and confidence · PRJEB28097_determinations.csv.gz (71.0 KB) — 11,793 evidence rows