Key Laboratory of Bioresources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, Sichuan, China.
Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China.
Microbiome. 2022 Feb 9;10(1):29. doi: 10.1186/s40168-021-01218-3.
Chronic diarrhea is a common disease causing morbidity and mortality of captive rhesus macaques (RMs, Macaca mulatta). Chronic diarrhea in RMs is typically characterized by long-term diarrhea and a weak response to antibiotic treatment. Diarrhea is also a common disease in humans and can cause death. However, the etiology of about half of diarrheal cases of humans is still unclear. Therefore, we performed shotgun metagenomic sequencing to characterize the differences in the gut microbiome and resistome of chronic diarrhea RMs and asymptomatic individuals.
Our results showed Lactobacillus spp. (mainly L. johnsonii, L. reuteri and L. amylovorus) were significantly depleted in chronic diarrhea RM guts compared to asymptomatic individuals (5.2 vs 42.4%). Functional annotation of genes suggested these Lactobacillus spp. carried genes involved in the adhesion of intestinal epithelial cells and production of bacteriocin. Chronic diarrhea RM guts also had a significantly greater abundance of many other gut bacteria, including mucin-degrading bacteria and opportunistic pathogens. The metabolic pathways of chronic diarrhea RM gut microbiome were enriched in aerobactin biosynthesis, while the metabolic pathways of asymptomatic RM gut microbiome were enriched in the production of short-chain fatty acids (SCFAs). Chronic diarrhea RM guts had a significantly greater abundance of antibiotic resistance genes (ARGs), such as ermF, aph(3')-IIIa, ermB, and floR. The strains isolated from feces and tissue fluid of chronic diarrhea RMs had higher resistance rates to the majority of tested antibiotics, but not cephamycin and carbapenem antibiotics. Gut microbial composition comparisons showed that several captive nonhuman primate (NHP) guts were more similar to the guts of humans with a non-westernized diet than humans with a westernized diet. Chronic diarrhea RM gut microbiome was strikingly similar to rural-living humans with diarrhea and humans with a non-westernized diet than asymptomatic RMs.
Our results suggested chronic diarrhea significantly altered the composition and metabolic pathways of the RM gut microbiome. The frequent use of antibiotics caused antibiotic resistance in chronic diarrhea RM gut microbiome with serious consequences for individual treatment and survival. The findings of this study will help us to improve the effective prevention and treatment of diarrhea in RMs. Video Abstract.
慢性腹泻是导致圈养猕猴（Macaca mulatta）发病和死亡的常见疾病。慢性腹泻的猕猴通常表现为长期腹泻，且对抗生素治疗的反应较弱。腹泻也是人类的一种常见疾病，也可能导致死亡。然而，人类约一半腹泻病例的病因仍不清楚。因此，我们进行了鸟枪法宏基因组测序，以描述慢性腹泻猕猴和无症状个体肠道微生物组和耐药组的差异。
我们的研究结果表明，与无症状个体相比，慢性腹泻猕猴肠道中乳杆菌属（主要是 L. johnsonii、L. reuteri 和 L. amylovorus）明显减少（5.2%比 42.4%）。基因功能注释表明，这些乳杆菌属携带与肠道上皮细胞黏附和细菌素产生相关的基因。慢性腹泻猕猴肠道中还存在许多其他肠道细菌，包括黏液降解菌和机会性病原体的丰度显著增加。慢性腹泻猕猴肠道微生物组的代谢途径富集了铁载体生物合成，而无症状猕猴肠道微生物组的代谢途径富集了短链脂肪酸（SCFAs）的产生。慢性腹泻猕猴肠道中抗生素耐药基因（ARGs）的丰度显著增加，如 ermF、aph(3')-IIIa、ermB 和 floR。从慢性腹泻猕猴粪便和组织液中分离的菌株对大多数测试抗生素的耐药率较高，但对头孢菌素和碳青霉烯类抗生素的耐药率较低。肠道微生物组成比较表明，与西方饮食的人类相比，一些圈养非人类灵长类（NHP）的肠道与非西方饮食的人类和腹泻患者的肠道更为相似。慢性腹泻猕猴肠道微生物组与腹泻的农村生活人类和无症状猕猴的肠道微生物组惊人地相似。
我们的研究结果表明，慢性腹泻显著改变了猕猴肠道微生物组的组成和代谢途径。抗生素的频繁使用导致慢性腹泻猕猴肠道微生物组产生抗生素耐药性，对个体治疗和生存产生严重后果。本研究的结果将有助于我们改善猕猴腹泻的有效预防和治疗。
