Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trials

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

doi:10.1016/j.ebiom.2024.105483

Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trials

EBioMedicine. 2024 Dec 7:111:105483. doi: 10.1016/j.ebiom.2024.105483. Online ahead of print.

Authors

Yuanqing Fu¹, Wanglong Gou², Haili Zhong³, Yunyi Tian², Hui Zhao², Xinxiu Liang², Menglei Shuai², Lai-Bao Zhuo³, Zengliang Jiang⁴, Jun Tang⁴, Jose M Ordovas⁵, Yu-Ming Chen⁶, Ju-Sheng Zheng⁷

Affiliations

¹ 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.
² Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, China.
³ Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China.
⁴ 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.
⁵ 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.
⁶ Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China. Electronic address: chenyum@mail.sysu.edu.cn.
⁷ 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. Electronic address: zhengjusheng@westlake.edu.cn.

PMID: 39647263
DOI: 10.1016/j.ebiom.2024.105483

Abstract

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.

Keywords: Gut microbiome; High-carbohydrate diet; Precision nutrition; n-of-1 trial.