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

ABSTRACT

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.

KEYWORDS:

• L. rhamnosus
• small intestine
• human
• metatranscriptome
• in situ gene expression
• probiotic fate

Disclosure statement

This author discloses the following: T. Smokvina and C. Chervaux are employees of Danone Nutricia Research. The remaining authors declare that they have no competing interests.

Availability of data and materials

The Metatranscriptome dataset supporting the conclusions of this article is available in the DANS repository, on the following doi: https://doi.org/10.17026/dans-xvh-yww8. The 16S data and the In vitro transcriptome data are available in the ENA repository under the following accession number: PRJEB61139 and PRJEB61087, respectively.

Ethics approval and consent to participate

This study was approved by the Medical Ethics Committee of Maastricht University (MU), Maastricht, the Netherlands, and performed in full accordance with the Declaration of Helsinki (latest amendment by the World Medic Association in Fortaleza, Brazil, in 2013) and Dutch Regulations on Medical Research involving Human Subjects (WMO, 1998), as well as with the International Conference on Harmonisation – Good Clinical Practice (ICH-GCP) guidelines. The study was performed at MU from 27 October 2016 (screening visit, first subject) until 27 October 2017 (last visit last subject). This study was registered in the US National Library of Medicine (http://www.clinicaltrials.gov, ID NCT NCT02920294). All subjects gave written informed consent before screening.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2244720

Additional information

Funding

This study was funded by Danone Research via an investigator grant (code: INSIDE:PLF-8712-GD). Study sponsor was not involved in the study design and in the collection, analysis, and interpretation of data nor in the decision to submit this work for publication.