Basal Diet Fed to Recipient Mice Was the Driving Factor for Colitis and Colon Tumorigenesis, despite Fecal Microbiota Transfer from Mice with Severe or Mild Disease

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• FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet.

• FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD.

• FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed.

• Western diet is characterized by high consumption of red meat, animal fat, and sugar, along with low fiber intake, and is considered a risk factor for many chronic diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC

• TWD enhanced symptoms of colitis; increased inflammation and injury to colon mucosa; altered inflammation and immune signaling in mucosal tissues; and promoted colon tumorigenesis in a murine model of colitis-associated colorectal cancer (CAC)

• Certain bacterial species have been shown to have pro-inflammatory properties by invading epithelial cells and inducing cytokine production, creating an ideal microenvironment for tumor development.

• whether the fecal microbiome associated with a Western diet enhances colitis symptoms, colon tumorigenesis, and microbiome modulation, when it is transferred into recipient mice fed either a healthy diet (AIN93G) or the total Western diet (TWD).

• AIN93G diet (AIN, cat. No. TD.94045), formulated to promote rodent health with an energy density of 3.8 kcal/g

• total Western diet (TWD, cat. No. TD.180497), the formulation of which was previously published [7], with an energy density of 4.4 kcal/g

• (1) fed AIN/fmt AIN, (2) fed AIN/fmt TWD, (3) fed TWD/fmt AIN, and (4) fed TWD/fmt TWD

• e TWD experienced a 5-fold increase in tumor multiplicity, a 5-fold increase in tumor volume, and an 11-fold increase in tumor burden (diet main effect, p < 0.0001), irrespective of FMT donor

• FMT from the AIN- or TWD-fed donors did not significantly alter tumor multiplicity or tumor burden, and FMT from the TWD-fed donors appeared to reduce average tumor volume

• We hypothesized that FMT from the donor mice that were fed the TWD and experienced severe colitis and high tumor burden would exacerbate symptoms of colitis and increase tumorigenesis in the recipient mice that were fed the AIN93G diet

• Conversely, we hypothesized that FMT from the donor mice that were fed the AIN93G diet and had mild colitis and low tumor burden would alleviate colitis symptoms and reduce tumorigenesis in the recipient mice that were fed the TWD.

• Modifiable lifestyle factors, such as the consumption of antibiotics, alcohol, or tobacco; the prevalence of chronic inflammatory disease; and diet can potentially change the gut microbiome

• BD patients typically have a lower microbial load, reduced diversity in their gut microbiome, an elevated abundance of pro-inflammatory taxa, and greater quantities of bacteria

• Hintze et al. depleted the gut microbiome of commonly used C57BL/6J mice with broad-scope antibiotics using this approach, followed by four weekly transfers of fecal material from two human donors; the authors found that the recipient mice’s microbiomes reflected approximately 68 to 75% of the human microbiome sequence mass [20]. We employed a similar antibiotic approach in a human-to-mouse FMT experiment in which fecal material from either obese or lean human donors was transferred to mice fed either a healthy diet, a high-fat diet, or a complete Western diet [21]. Interestingly, we found that the diet fed to the recipient mice was the driving force in shaping the gut microbiome of the recipient mice as opposed to the source of the donated microbiota.