# Study of Fecal Microbiota Transplantation Ameliorates Colon Morphology and Microbiota Function in High-Fat Diet Mice

## TL;DR

Fecal microbiota transplantation from normal diet mice improves gut health and reduces weight gain in mice fed a high-fat diet.

## Contribution

This study provides mechanistic insights into how FMT restores gut microbiota and host metabolism under high-fat diet stress.

## Key findings

- FMT reduced HFD-induced weight gain and normalized digestive enzyme activity.
- FMT improved intestinal architecture and upregulated gut barrier proteins like MUC2 and Claudin-1.
- FMT increased beneficial microbes like Lactobacillus and Bifidobacterium while reducing pathogens.

## Abstract

Fecal microbiota transplantation can enhance the diversity of gut microbes and modulate dominant microbial populations, thereby facilitating the restoration of disrupted gut microbiota and playing an essential role in the recovery of mucosal barrier function. The biological advantages highlighted in our study include the regulation of gut microbiota composition, stimulation of intestinal motility, maintenance of microecological homeostasis, reduction in inflammatory responses, and enhancement of gastrointestinal functional capacity. Our experimental findings indicated that when fecal microbiota from A Normal Diet Group were administered concurrently with a high-fat diet, there was a notable promotion in the restoration of several core physiological parameters. These included equilibrium in body mass, activity of digestive enzymes, structure of colon histoarchitecture, and functions related to microbial metabolism. This therapeutic approach not only supported an increase in populations of beneficial endogenous probiotics but also effectively suppressed pathways associated with inflammation caused by pathogens. Moreover, our microbiome analysis revealed that fecal microbiota transplantation from a normal diet led to a significant rise in the populations of beneficial symbiotic microorganisms. This enhancement was achieved through the improvement of nutritional metabolic networks and optimization of environmental signal transduction systems, in addition to advancing maturation of the mucosal layer. Importantly, we demonstrated that fecal microbiota transplantation from a normal dietary source effectively alleviated enteric dysfunction associated with high-fat diet consumption. This intervention reinforced the integrity of the gut barrier by facilitating microbiota-mediated adjustments in epithelial tight junction complexes and mechanisms involved in mucin biosynthesis.

This study investigates whether fecal microbiota transplantation (FMT) can alleviate gut microbiota dysbiosis induced by a high-fat diet (HFD) through modulation of fatty acid metabolism, competition for nutrients, production of short-chain fatty acids (SCFAs), and restoration of mucus layer integrity. To elucidate the mechanisms by which FMT regulates colonic microbial function and host metabolic responses, 80 male Bal b/c mice were randomly assigned to four experimental groups (n = 20 per group): Normal Diet Group (NDG), High-Fat Diet Group (HDG), Restrictive Diet Group (RDG), and HDG recipients of NDG-derived fecal microbiota (FMT group). The intervention lasted for 12 weeks, during which body weight was monitored biweekly. At the end of the experiment, tissue and fecal samples were collected to assess digestive enzyme activities, intestinal histomorphology, gene expression related to gut barrier function, and gut microbiota composition via 16S rRNA gene sequencing. Results showed that mice in the HDG exhibited significantly higher final body weight and greater weight gain compared to those in the NDG and RDG (p < 0.05). Notably, FMT treatment markedly attenuated HFD-induced weight gain (p < 0.05), reducing it to levels comparable with the NDG (p > 0.05). While HFD significantly elevated the activities of α-amylase and trypsin (p < 0.05), FMT supplementation effectively suppressed these enzymatic activities (p < 0.05). Moreover, FMT ameliorated HFD-induced intestinal architectural damage, as evidenced by significant increases in villus height and the villus height-to-crypt depth ratio (V/C) (p < 0.05). At the molecular level, FMT significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-1α, TNF-α) and upregulated key tight junction proteins (Occludin, Claudin-1, ZO-1) and mucin-2 (MUC2) relative to the HDG (p < 0.05). 16S rRNA analysis demonstrated that FMT substantially increased the abundance of beneficial genera such as Lactobacillus and Bifidobacterium while reducing opportunistic pathogens including Romboutsia (p < 0.05). Furthermore, alpha diversity indices (Chao1 and ACE) were significantly higher in the FMT group than in all other groups (p < 0.05), indicating enhanced microbial richness and community stability. Functional prediction using PICRUSt2 revealed that FMT-enriched metabolic pathways (particularly those associated with SCFA production) and enhanced gut barrier-related functions. Collectively, this study deepens our understanding of host–microbe interactions under HFD-induced metabolic stress and provides mechanistic insights into how FMT restores gut homeostasis, highlighting its potential as a therapeutic strategy for diet-induced dysbiosis and associated metabolic disorders.