Effect of diet and intestinal AhR expression on fecal microbiome and metabolomic profiles
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Microbial Cell Factories Open Access
RESEARCH
Effect of diet and intestinal AhR expression on fecal microbiome and metabolomic profiles Fang Yang1, Jennifer A. A. DeLuca2, Rani Menon1, Erika Garcia‑Vilarato2, Evelyn Callaway1, Kerstin K. Landrock2, Kyongbum Lee3, Stephen H. Safe4, Robert S. Chapkin2, Clinton D. Allred2 and Arul Jayaraman1,5*
Abstract Background: Diet, loss of aryl hydrocarbon receptor (AhR) expression and their modification of the gut micro‑ biota community composition and its metabolites affect the development of colorectal cancer (CRC). However, the concordance between fecal microbiota composition and the fecal metabolome is poorly understood. Mice with specific AhR deletion (AhRKO) in intestinal epithelial cell and their wild-type littermates were fed a low-fat diet or a high-fat diet. Shifts in the fecal microbiome and metabolome associated with diet and loss of AhR expression were assessed. Microbiome and metabolome data were integrated to identify specific microbial taxa that contributed to the observed metabolite shifts. Results: Our analysis shows that diet has a more pronounced effect on mouse fecal microbiota composition than the impact of the loss of AhR. In contrast, metabolomic analysis showed that the loss of AhR in intestinal epithelial cells had a more pronounced effect on metabolite profile compared to diet. Integration analysis of microbiome and metabolome identified unclassified Clostridiales, unclassified Desulfovibrionaceae, and Akkermansia as key contribu‑ tors to the synthesis and/or utilization of tryptophan metabolites. Conclusions: Akkermansia are likely to contribute to the synthesis and/or degradation of tryptophan metabolites. Our study highlights the use of multi-omic analysis to investigate the relationship between the microbiome and metabolome and identifies possible taxa that can be targeted to manipulate the microbiome for CRC treatment. Keywords: Diet, AhR, Tryptophan metabolites, Akkermansia Background Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States [1]. Many factors, such as diet, physical activity, smoking, and alcohol use, contribute to CRC risk; among these, diet is the most important as it accounts for 80% of CRC incidence [2]. Previous studies have shown that a diet high in saturated fat increases the risk for the development of CRC [3–5], and a higher intake of a Western diet has also been linked to an increased risk of *Correspondence: [email protected] 1 Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA Full list of author information is available at the end of the article
CRC re-occurrence [6]. Epidemiological and scientific studies show that the increased risk of CRC associated with low dietary fiber intake is related to alterations in the composition of the colonic microbiota and its metabolic activity [7]. The microbiota associated with a low-fiber and high-fat diet in humans is enriched for taxa that produce pro-inflammatory and/ or carcinogenic met
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