# Synergistic effects of Clostridium butyricum and Akkermansia muciniphila-derived postbiotics ameliorate DSS-induced colitis and associated tumorigenesis through immunomodulation and microbiota regulation in mice

## TL;DR

This study shows that a postbiotic mix from two gut bacteria helps reduce inflammation and cancer in the colon by improving gut health and immune response in mice.

## Contribution

The study introduces a novel postbiotic formulation with synergistic effects for treating IBD and CRC.

## Key findings

- SupCBAKK significantly alleviated IBD and CRC symptoms in mice.
- SupCBAKK synergized with anti-PD-L1 to enhance antitumor immune responses.
- The formulation repaired mucosal barriers and improved gut microbiota balance.

## Abstract

Inflammatory bowel disease (IBD) is a major precursor to colorectal cancer (CRC). Our previous study demonstrated that combined administration of the probiotics Clostridium butyricum (CB) and Akkermansia muciniphila (AKK) significantly alleviated IBD and CRC symptoms in mice. Increasing evidence suggests that probiotic metabolites (postbiotics) offer significant advantages in disease prevention and treatment without the stability and safety concerns associated with live bacterial therapies. To further explore the therapeutic potential of CB- and AKK-fermented metabolites against IBD and CRC, we established a DSS-induced IBD model and DSS/AOM-induced CRC orthotopic models in mice and evaluated the effects of CB and AKK metabolites on alleviating IBD and CRC. The results revealed that the fermented metabolites of CB and AKK (designated as SupCB and SupAKK, respectively) exhibited significant synergistic effects. Mixed fermented metabolites (designated as SupCBAKK) outperformed individual metabolites, significantly alleviating IBD and CRC symptoms by modulating immune responses, repairing the mucosal barrier, and ameliorating gut dysbiosis. Notably, SupCBAKK synergized with the immune checkpoint inhibitor anti-PD-L1 (aPD-L1), enhancing tumor sensitivity to immunotherapy and amplifying antitumor immune responses. These findings underscore the potential of SupCBAKK as a novel postbiotic formulation for mitigating IBD and CRC progression and offer innovative strategies for developing CB- and AKK-based therapeutic interventions.

This study highlights the therapeutic potential of SupCBAKK, a novel postbiotic formulation derived from the combined fermentation metabolites of CB and AKK, IBD, and colitis-associated colorectal cancer through the modulation of gut microbiota and immunometabolism.