Dietary Tryptophan‐Lactobacillus rhamnosus GG Interactions Modify Intestinal Differentiation and Function

• DOI: 10.1096/fasebj.2022.36.s1.r3102
• Publication Date: 2022-05-03T08:23:48Z
• Authors: Panan Suntornsara...; Juan Flores; Ravij Upadhyay; Paula Lopez; Radha Patel; Sheila Bandyopadhyay; Nan Gao; Ronaldo Ferraris
• Keywords: Lactobacillus reuteri; Lactobacillus rhamnosus; Mucin 2

Although the influence of gut microbiota on structure and proliferation intestinal epithelial cells has been established, there is disconcordance information related to cell type differentiation, because most studies probiotics reflected an outcome from interactions among Lactobacillus, numerous existing microbes, host, with limited insight specific impact Lactobacilli spp. For example, L. reuteri enhanced goblet Paneth differentiation in intestine conventionally-raised chickens established commensal microbiota, confounding results. Here we fed gnotobiotic mice tryptophan (t+) or trp-free (t-) diets, followed by monocolonization LGG (L+, ATCC 53103) without (control, L-) for a total 4 groups (L+t+, L+t-, L-t+, L-,t-), then ileum transcriptome was analyzed 3 wk later. L- remained germ-free throughout while only associated L+. Principal component analysis shows L+ t+ itself modestly cluster away L-t-, but depicting combination L+t+ far removed others. The heatmap whole several distinct genes affected alone. However, simultaneous dramatically upregulates gene clusters downregulating few. Volcano plots Venn diagrams comparing L-t- L+t- indicate ~2300 unique (LGG) (tryptophan) Comparisons between (effect t L) L-t+ L t) each >3800 genes, suggesting that synergistic primarily underlie probiotic ascribed dietary t. Many upregulated have functions typical mature enterocytes: tight junctions, brush border membrane transporters enzymes, bile acid metabolism, lipid synthesis fatty b-oxidation. downregulated are antimicrobial secreted peptides differentiated cells. This latter result recapitulated when reexamined conventional perfused h LGG, as expression many defensins decreased >10-fold, not this probiotic's effects can arise both acute ex vivo chronic also hosts housing complex microbiota. Remarkably, Notch ligands Dll1 Dll4 typically expressed well Yap1, Axin2 Ctnnb1 ileum, downstream upregulation Hes1 repression Atoh1, leading suppression secretory lineage. In conclusion, may lead t+-derived metabolites host bacteria, enhancement absorptive enterocyte those