# Fecal Microbiota Transplantation Attenuates Inflammation Through TGF-β1/Smad Signaling Pathway in Caco-2 and RAW264.7 Cells

## TL;DR

Fecal microbiota transplantation reduces inflammation in intestinal cells by affecting the TGF-β1/Smad signaling pathway.

## Contribution

The study reveals how FMT reduces inflammation via the TGF-β1/Smad pathway in intestinal and macrophage cells.

## Key findings

- FMT downregulated TGF-β1, Smad2, and Smad3 expression in modified Caco-2 cells.
- FMT increased Smad7 expression and reduced Smad2/Smad3 phosphorylation.
- Modulating the TGF-β1/Smad pathway could improve FMT outcomes for UC patients.

## Abstract

Ulcerative colitis (UC) represents a persistent inflammatory condition that influences millions of people worldwide, with rising prevalence and limited treatment options. Current therapies, such as corticosteroids and immunosuppressants, offer symptom relief but are associated with significant adverse effects. Fecal microbiota transplantation (FMT) is being increasingly viewed as an effective alternative, but the molecular basis for its benefits in UC is still not fully understood. This study aimed to explore the function of the transforming growth factor-beta 1 (TGF-β1)/Smad signaling cascade in FMT-induced remission of UC.

Stable Smad3-knockdown and Smad3-overexpression Caco2 cell lines were established via lentivirus-mediated transduction. These modified Caco-2 cells were co-incubated with RAW264.7 macrophages to mimic intestinal inflammation in vitro. Following FMT treatment, the expression of major components of the TGF-β1/Smad signaling cascade was assessed.

The results demonstrated that FMT markedly downregulated TGF-β1, Smad2, and Smad3 expression, while enhancing Smad7 expression in both Smad3-knockdown and overexpression cell lines. In addition, FMT treatment attenuated the phosphorylation of Smad2 and Smad3, indicating a decrease in the activation of the TGF-β1/Smad signaling pathway.

These findings show that by optimizing FMT treatments to focus on the specific pathway, an improvement of therapeutic outcomes can be achived for UC patients.