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.

中文翻译：

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幽门螺杆菌感染与肠道微生物组和代谢组改变有关，使高脂饮食小鼠血糖调节受损

摘要

新兴证据表明，幽门螺杆菌感染与代谢紊乱有关，尽管其潜在机制尚不清楚。这项研究旨在调查幽门螺杆菌，高脂饮食（HFD）和肠道菌群与葡萄糖调节和微生物代谢产物变化之间的相互作用。将小鼠随机分配到喂食饮食或HFD的幽门螺杆菌感染和未感染组。4周后，对两个HFD组给予抗生素鸡尾酒8周，以消除肠道菌群。结果表明，HFD显着促进了体重增加，胰岛素抵抗和葡萄糖耐量下降，这些在抗生素治疗后已减轻至正常水平。幽门螺杆菌感染加剧了HFD引起的高血糖症，无法通过抗生素恢复。与单独施用幽门螺杆菌或HFD的小鼠相比，接受幽门螺杆菌和HFD（HFDHp）处理的小鼠肠道菌群的扰动更大，多样性下降，幽门螺杆菌的丰度较高，而幽门螺杆菌的丰度较低。乳杆菌。此外，与单独使用HFD的组相比，HFDHp组的肠道菌群更容易受到抗生素破坏，而克雷伯菌的多样性和优势极低。粪便代谢组学分析表明幽门螺杆菌的结合感染和HFD改变了代谢成分和功能，这与葡萄糖失调有关。幽门螺杆菌感染可能会加剧由HFD引起的肠道微环境的营养不良，包括微生物群和代谢产物的改变，这会削弱抗生素的修复作用并导致葡萄糖异常的持续存在。

关键点

•首先探讨了Hp，HFD和抗生素对葡萄糖代谢的相互作用。

•Hp感染削弱了抗生素对HFD诱导的葡萄糖失调的作用。

•Hp感染改变了肠道微生物群和代谢物，而HFD加重了肠道菌群和代谢物。