Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
Yuanqing Fu,
Wanglong Gou,
Haili Zhong,
Yunyi Tian,
Hui Zhao,
Xinxiu Liang,
Menglei Shuai,
Lai-Bao Zhuo,
Zengliang Jiang,
Jun Tang,
Jose M. Ordovas,
Yu-ming Chen,
Ju-Sheng Zheng
Affiliations
Yuanqing Fu
Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, China; Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China
Wanglong Gou
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China
Haili Zhong
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China
Yunyi Tian
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China
Hui Zhao
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China
Xinxiu Liang
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China
Menglei Shuai
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China
Lai-Bao Zhuo
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China
Zengliang Jiang
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China; Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
Jun Tang
Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China; Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China
Jose M. Ordovas
Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; Nutritional Genomics and Epigenomics Group, Precision Nutrition and Obesity Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain; Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Institute of Health Carlos III, Madrid, Spain
Yu-ming Chen
Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China; Corresponding author.
Ju-Sheng Zheng
Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, China; Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China; Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China; Corresponding author. School of Medicine, Westlake University, Hangzhou, China.
Summary: Background: The interplay between diet and gut microbiome substantially influences host metabolism, but uncertainties remain regarding their relationships tailored for each subject given the huge inter-individual variability. Here we aim to investigate diet-gut microbiome interaction at single-subject resolution and explore its effects on blood glucose homeostasis. Methods: We conducted a series of nutritional n-of-1 trials (NCT04125602), in which 30 participants were assigned high-carbohydrate (HC) and low-carbohydrate (LC) diets in a randomized sequence across 3 pair of cross-over periods lasting 72 days. We used shotgun metagenomic sequencing and continuous glucose monitoring systems to profile the gut microbiome and blood glucose, respectively. An independent cohort of 1219 participants with available metagenomics data are included as a validation cohort. Findings: We demonstrated that the gut microbiome exhibited both intra-individually dynamic and inter-individually personalized signatures during the interventions. At the single-subject resolution, we observed person-specific response patterns of gut microbiota to interventional diets. Furthermore, we discovered a personal gut microbial signature represented by a carb-sensitivity score, which was closely correlated with glycemic phenotypes during the HC intervention, but not LC intervention. We validate the role of this score in the validation cohort and find that it reflects host glycemic sensitivity to the personal gut microbiota profile when sensing the dietary carbohydrate inputs. Interpretation: Our finding suggests that the HC diet modulates gut microbiota in a person-specific manner and facilitates the connection between gut microbiota and glycemic sensitivity. This study represents a new paradigm for investigating the diet–microbiome interaction in the context of precision nutrition. Funding: This work was supported by the National Key R&D Program of China, National Natural Science Foundation of China and Zhejiang Provincial Natural Science Foundation of China.
