Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
State Key Laboratory of Animal Nutrition, Key Laboratory of Animal Genetics Breeding and Reproduction of Ministry of Agriculture and Rural Affairs of China, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, China.
Microbiol Spectr. 2022 Aug 31;10(4):e0071722. doi: 10.1128/spectrum.00717-22. Epub 2022 Jul 7.
Several studies have suggested a role for gut mucosa-associated microbiota in the development of obesity, but the mechanisms involved are poorly defined. Here, the impact of the gut mucosa-associated microbiota on obesity and related metabolic disorders was evaluated in a metabolic syndrome (MetS) porcine model. Body composition was determined among male Wuzhishan minipigs consuming a high-energy diet (HED) and compared to that of those consuming a normal diet (ND), and gut segments (duodenum, jejunum, ileum, cecum, colon, and rectum) were sampled for paired analysis of mucosa-associated microbiota and transcriptome signatures with 16S rRNA gene and RNA sequencing, respectively. Our data indicated that long-term HED feeding significantly increased body weight and visceral fat deposition and aggravated metabolic disorders. Specially, HED feeding induced mucosa-associated microbiota dysbiosis and selectively increased the abundance of the families , , and in the upper intestine. The association analysis indicated that specific bacteria play key roles in adiposity, e.g., Lactobacillus johnsonii in the duodenum, Actinobacillus indolicus in the jejunum, Acinetobacter johnsonii in the ileum, Clostridium butyricum in the cecum, Haemophilus parasuis in the colon, and bacterium NLAEzlP808, , and sp. JNUH029 in the rectum. Transcriptome data further revealed intestinal lipid metabolism and immune dysfunction in the MetS individuals, which may be associated with obesity and related metabolic disorders. Our results indicated that gut mucosa-associated microbiota dysbiosis has the potential to exacerbate obesity, partially through modulating systemic inflammatory responses. Obesity is a major risk factor for metabolic syndrome, which is the most common cause of death worldwide, especially in developed countries. The link between obesity and gut mucosa-associated microbiota is unclear due to challenges associated with the collection of intestinal samples from humans. The current report provides the first insight into obesity-microbiome-gut immunity connections in a metabolic syndrome (MetS) porcine model. The present results show that dysbiosis of mucosal microbiota along the entire digestive tract play a critical role in the proinflammatory response in the host-microbial metabolism axis, resulting in obesity and related metabolic disorders in the MetS model.
几项研究表明，肠道黏膜相关微生物群在肥胖的发展中起作用，但涉及的机制尚未明确。在这里，我们评估了肠道黏膜相关微生物群对代谢综合征（MetS）猪模型肥胖及相关代谢紊乱的影响。我们测定了食用高能饮食（HED）的雄性五指山小型猪的体成分，并与食用正常饮食（ND）的猪进行了比较，同时对肠道各段（十二指肠、空肠、回肠、盲肠、结肠和直肠）进行了取样，分别采用 16S rRNA 基因和 RNA 测序进行黏膜相关微生物群和转录组特征的配对分析。我们的数据表明，长期 HED 喂养显著增加了体重和内脏脂肪沉积，并加重了代谢紊乱。特别地，HED 喂养诱导了黏膜相关微生物群失调，并选择性地增加了上消化道中 、 和 科的丰度。关联分析表明，特定细菌在肥胖中发挥关键作用，例如，十二指肠中的约翰逊乳杆菌、空肠中的吲哚乙酸菌、回肠中的醋酸杆菌、盲肠中的丁酸梭菌、结肠中的副猪嗜血杆菌以及直肠中的 NLAEzlP808、 和 sp. JNUH029。转录组数据进一步揭示了 MetS 个体的肠道脂质代谢和免疫功能障碍，这可能与肥胖和相关代谢紊乱有关。我们的结果表明，肠道黏膜相关微生物群失调有可能通过调节全身炎症反应来加重肥胖。肥胖是代谢综合征的一个主要危险因素，尤其是在发达国家，代谢综合征是全球最常见的死亡原因。由于从人类肠道中收集肠道样本存在挑战，肥胖与肠道黏膜相关微生物群之间的联系尚不清楚。本报告首次提供了代谢综合征猪模型中肥胖-微生物群-肠道免疫联系的见解。本研究结果表明，整个消化道黏膜微生物群的失调在宿主-微生物代谢轴的促炎反应中起着关键作用，导致 MetS 模型中的肥胖和相关代谢紊乱。
