# Postbiotic Metabolites from a 31-Strain Lactobacillus/Bifidobacterium Co-Culture Attenuate DSS Colitis with Barrier- and Circadian-Linked Transcriptomic Signatures

## TL;DR

A fermented soy extract made from beneficial bacteria reduces gut inflammation in mice, potentially offering a food-based strategy for preventing intestinal diseases.

## Contribution

The study introduces a fermented soy extract containing postbiotic metabolites that protect against colitis through multiple biological mechanisms.

## Key findings

- The fermented soy extract reduced colitis symptoms, preserved colon length, and improved tissue health in mice.
- Transcriptomic analysis revealed strengthened gut barrier function and reduced inflammation in treated mice.
- The extract altered gut microbiota, increasing beneficial bacteria and decreasing harmful ones.

## Abstract

Ulcerative colitis is a chronic inflammatory disease of the large intestine that can cause diarrhea, bleeding, and abdominal pain. Safe, food-based approaches that help prevent flare-ups are strongly needed. In this study, we tested whether small molecules made during fermentation of soy by a mix of beneficial bacteria (without including any live bacteria) could protect the gut. Mice received this fermented soy extract before and during chemically induced colitis. Compared with untreated colitis mice, treated mice had milder disease symptoms, maintained longer colons, and showed clearer improvement in intestinal tissue damage under the microscope. Blood analyses indicated that immune messenger proteins shifted in a direction consistent with reduced inflammation. Gene activity patterns in the rectum suggested strengthened mucus and barrier functions and a calmer tissue repair state. In addition, the fermented soy extract changed the gut microbial community, increasing several bacteria often associated with gut health and reducing potentially harmful bacteria. These findings suggest that fermentation-derived bacterial metabolites may support intestinal barrier function and immune balance and may be useful as a preventive dietary strategy for maintaining gut health in inflammatory bowel conditions.

Postbiotics produced by beneficial bacteria are emerging as safe dietary approaches to intestinal inflammation. We evaluated intestinal bacterial metabolites (IBM), a cell-free fermented soybean extract generated by co-culturing 31 Lactobacillus/Bifidobacterium-related strains, for prophylactic protection in 3% dextran sulfate sodium (DSS)-induced colitis. Male C57BL/6NJ mice received oral IBM (0.4 or 2 mL/kg/day) or vehicle for 7 days before and during 7 days of DSS. Disease activity index (DAI), colon length, and histopathology were assessed, and endpoint serum cytokines were quantified by a multiplex bead assay. DSS-independent responses were examined in healthy mice after 7 days of IBM by rectal RNA sequencing and cecal 16S rDNA profiling, and direct epithelial effects were tested in HCT-116 and DLD-1 cells treated with 2% IBM. IBM attenuated colitis, improving DAI, preventing colon shortening, and ameliorating histopathology, with decreased IL-23 and IL-17A and increased IFN-β and GM-CSF. Rectal transcriptomics showed modulation of circadian programs, upregulation of mucosal/barrier genes, and reduced extracellular-matrix remodeling signatures. IBM increased junctional proteins and barrier-related transcripts in vitro and shifted the microbiota, increasing Lactobacillus and Roseburia while decreasing Streptococcus and Staphylococcus. These coordinated clinical, immunological, transcriptomic, epithelial, and microbiome changes support prophylactic protection by IBM against DSS colitis.