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Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of  Lacticaseibacillus rhamnosus  CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the  in situ  transcriptome of  L. rhamnosus  in the small intestine, which was contrasted with transcriptome data obtained from  in vitro  cultivation. These comparative analyses revealed substantial metabolic adaptations of  L. rhamnosus  during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of  L. rhamnosus  in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem’s overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed  in situ  by  L. rhamnosus  (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem’s activity profile. This study establishes the survival capacity of  L. rhamnosus  in the human small intestine and highlights its functional adjustment  in situ , which we postulate to play a role in the probiotic effects associated with this strain.

L. rhamnosus CNCM I-3690 survival, adaptation, and small bowel microbiome impact in human