Abstract
Emerging evidence suggests that Helicobacter pylori infection is associated with metabolic disorders, although the underlying mechanisms are poorly defined. This study aimed to investigate the interaction among H. pylori, a high-fat diet (HFD), and the gut microbiota with glucose regulation and alterations in microbial metabolites. Mice were randomly allocated to H. pylori-infected and noninfected groups fed a chow diet or an HFD. After 4 weeks, two of the HFD groups were given antibiotic cocktails for 8 weeks to eliminate the gut microbiota. The results showed that an HFD significantly promoted increases in body weight, insulin resistance, and glucose intolerance, which were alleviated to normal after antibiotic treatment. H. pylori infection aggravated HFD-induced hyperglycemia, which could not be restored by antibiotics. The perturbation of the gut microbiota was greater in the mice cotreated with H. pylori and an HFD (HFDHp) compared to those administered either H. pylori or an HFD alone, with a loss of diversity, higher abundance of Helicobacter, and lower abundance of Lactobacillus. Furthermore, compared to that of the HFD alone group, the gut microbiota of the HFDHp group was much more susceptible to antibiotic destruction, with extremely lower diversity and dominance of Klebsiella. Fecal metabolome analyses demonstrated that the combination of H. pylori infection and an HFD altered metabolic composition and function, which were linked to glucose dysregulation. H. pylori infection may exacerbate the dysbiosis of the gut microenvironment induced by an HFD, including alterations in the microbiota and metabolites, which weakens the restorative effect of antibiotics and results in the persistence of glucose disorders.
Key points
• The interplay of Hp, HFD, and antibiotics on glucose metabolism was firstly explored.
• Hp infection impaired the effect of antibiotics on HFD-induced glucose dysregulation.
• Hp infection altered gut microbiota and metabolites which aggravated by HFD.
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Data availability
The accession numbers for the metabolomics data reported in this study are MetaboLights: MTBLS2037. The accession number for the 16S rRNA datasets containing the analysis of gut microbiota is SRA: SRP279066.
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Acknowledgements
The authors thank Dr. Zhongming Ge (Division of Comparative Medicine, Massachusetts Institute of Technology, USA) for the kind gift of the H. pylori strain PMSS1.
Funding
This work was supported by the National Natural Science Foundation of China (no. 81860106, 81670507, and 81870395), grants from the Science and Technology Department of Jiangxi Province (no. 20192BBG70037), and the grants from the Nanchang University (no. PY201816).
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CH conceived and designed research. CP, XX, and YO conducted experiments. XX and ZH collected the samples. CP, NSL, and CH analyzed and visualized data. CP and CH wrote the manuscript. YZ and NHL supervised and revised the manuscript. All authors read and approved the manuscript.
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Chao Peng and Xinbo Xu joint first co-authorship.
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Peng, C., Xu, X., He, Z. et al. Helicobacter pylori infection worsens impaired glucose regulation in high-fat diet mice in association with an altered gut microbiome and metabolome. Appl Microbiol Biotechnol 105, 2081–2095 (2021). https://doi.org/10.1007/s00253-021-11165-6
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DOI: https://doi.org/10.1007/s00253-021-11165-6