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

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 si...

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Main Authors: 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
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Language:English
Published: Elsevier 2025-01-01
Series:EBioMedicine
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Online Access:http://www.sciencedirect.com/science/article/pii/S235239642400519X
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author 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
author_facet 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
author_sort Yuanqing Fu
collection DOAJ
description 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.
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spelling doaj-art-8befb163e2ea4ffbb6c661a688d743a32025-08-20T02:20:42ZengElsevierEBioMedicine2352-39642025-01-0111110548310.1016/j.ebiom.2024.105483Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in contextYuanqing Fu0Wanglong Gou1Haili Zhong2Yunyi Tian3Hui Zhao4Xinxiu Liang5Menglei Shuai6Lai-Bao Zhuo7Zengliang Jiang8Jun Tang9Jose M. Ordovas10Yu-ming Chen11Ju-Sheng Zheng12Affiliated 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, ChinaZhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, ChinaDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, ChinaZhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, ChinaZhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, ChinaZhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, ChinaZhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, ChinaDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, ChinaZhejiang 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, ChinaZhejiang 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, ChinaNutrition 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, SpainDepartment of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S235239642400519XPrecision nutritionHigh-carbohydrate dietGut microbiomen-of-1 trial
spellingShingle 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
Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
EBioMedicine
Precision nutrition
High-carbohydrate diet
Gut microbiome
n-of-1 trial
title Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
title_full Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
title_fullStr Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
title_full_unstemmed Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
title_short Diet-gut microbiome interaction and its impact on host blood glucose homeostasis: a series of nutritional n-of-1 trialsResearch in context
title_sort diet gut microbiome interaction and its impact on host blood glucose homeostasis a series of nutritional n of 1 trialsresearch in context
topic Precision nutrition
High-carbohydrate diet
Gut microbiome
n-of-1 trial
url http://www.sciencedirect.com/science/article/pii/S235239642400519X
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