Authors
Nachman, E. J., Somasundaram, L. N., Ardis, A. K., Ramani, S., Britton, R. A.
Abstract
The human small intestine (SI) microbiome is a dynamic ecosystem that engages in complex interactions with the host, including those mediated by diet, hormones, and immune systems. However, the cultivation and characterization of small intestinal microbial therapeutics have yet to be developed. One reason for their limited progress may be that previous microbes were derived from other environments, including food, stool, and breast milk, rather than directly from their native environment, the human SI. Therefore, we investigated the human SI as a relevant source and vital target for the development of future microbial therapeutics for SI diseases. We isolated 10 unique Lactobacillaceae isolates from six different species from samples spanning the upper gastrointestinal tract of five organ donors. We performed whole-genome sequencing analysis and assessed the viability of isolates after numerous GI-like stresses. Next, we examined the ability of the isolates to stimulate enteric hormone secretion, modulate pro-inflammatory cytokines, and influence the replication of a live, attenuated oral rotavirus vaccine strain. We observed that SI Lactobacillaceae strains can survive GI-related stresses like other commercialized lactobacilli. Certain isolates were able to promote secretion of the hormones secretin and oxytocin from ex-vivo adult tissue and human infant intestinal organoids. In addition, we found strains that were able to modulate TNF secretion from the human monocytoid line THP-1. Finally, we found that L. rhamnosus strain 103 (Lr 103) significantly promoted antiviral IFN-{lambda} secretion via TLR3 by secreted RNA in infant organoids. Lr 103, restricted rotavirus vaccine strain replication in infant organoids.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Aug 2026.
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