Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health

Authors: HUDA, M - University Of California, Davis; SALVADOR, ANNA - Texas A&M University; BARRINGTON, WILLIAM - Texas A&M University; GACASAN, C - Texas A&M University; D'SOUZA, EDELINE - University Of Surrey; DEUS RAMIREZ, LAURA - University Of Surrey; THREADGILL, DAVID - Texas A&M University; Bennett, Brian

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/11/2022
Publication Date: 8/18/2022
Citation: Huda, M.N., Salvador, A.C., Barrington, W.T., Gacasan, C.A., D'Souza, E.M., Deus Ramirez, L., Threadgill, D.W., Bennett, B.J. 2022. Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health. Frontiers in Nutrition. 9. Article 896348. https://doi.org/10.3389/fnut.2022.896348.
DOI: https://doi.org/10.3389/fnut.2022.896348

Interpretive Summary: Metabolic diseases are major public health issues worldwide. A Western diet (WD) is believed to be a contributor to the global metabolic diseases epidemic. In contrast, the traditional Mediterranean diet (MeD), Ketogenic diet (KD), and Japanese diet (JD) are considered beneficial for metabolic health. In this study, we took an integrative approach to understand how genetics, diet, and gut microbiota affect host metabolic health. We treated four widely used metabolically diverse inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ) with four human-relevant diets (MeD, JD, KD, WD), and a control mouse chow for 24 weeks. We also found Depending on the host genetics and gut microbiota, the same diet could have different metabolic health effects. Overall, our study demonstrated that both host genetics and gut microbiota need to be considered during the development of approaches for precision nutrition to improve metabolic health.

Technical Abstract: Metabolic diseases are major public health issues worldwide and are responsible for disproportionately higher healthcare costs and increased complications of many diseases including Coronavirus Disease 2019. A Western diet (WD) pattern is believed to be a contributor to the global metabolic diseases’ epidemic. In contrast the Mediterranean diet (MeD), Ketogenic diet (KD), and Japanese diet (JD) patterns are considered beneficial for metabolic health. However, the effect of diet on metabolic health varies depending on several factors including host genetics. Additionally, dysbiosis (altered gut microbiota) also has been found responsible for poor metabolic health. Therefore, an integrative approach is needed to study how genetics, diet, and gut microbiota affect host’s metabolic health to understand the underlying mechanisms of interindividual variation in the propensity to develop metabolic diseases. To understand the complex relationship between host genetics, gut microbiota and dietary patterns, we treated four widely used metabolically-diverse inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ) with four human relevant diets (MeD, JD, KD, WD), and a control mouse chow from 6 weeks to 30 weeks of age. We found that diet-induced alteration of gut microbiota is significantly modified by host genetic architecture. Depending on the gut microbiota, the same diet could have different metabolic health effects. Our study also revealed that C57BL/6J mice are more susceptible to dysbiosis compared to other mice in this study indicating that host genetics is an important modulator of the diet-microbiota-metabolic health axis. Overall, our study demonstrated complex interactions between host genetics, gut microbiota, and diet on metabolic health; thus, both host genetics and gut microbiota need to be considered during development of approaches for precision nutrition to improve metabolic health.