Amimo Joshua O, Kunyanga C N, Raev S A, Kick M, Micheal H, Saif L J, Vlasova Anastasia N
Center for Food Animal Health, Department of Animal Sciences, College of Food, Agricultural and Environmental Sciences, The Ohio State University, 1680 Madison Avenue, Wooster, OH, 44691, USA.
Department of Food Science, Nutrition and Technology, Faculty of Agriculture, University of Nairobi, P.O Box 29053, Nairobi, 00625, Kenya.
Gut Pathog. 2025 Jun 25;17(1):49. doi: 10.1186/s13099-025-00723-2.
As robust animal models to study the pathophysiology of stunting are absent, we have comparatively characterized the gut microbiota of malnourished/stunted vs. clinically healthy/normal Kenyan toddlers (12-24 months old) and established a gnotobiotic (Gn) pig fecal transplant model to gain understanding of microbial community structure associated with stunting. As expected, the bacterial composition between the two toddler groups was distinct: Actinobacteria was most prevalent in healthy toddlers, whereas Proteobacteria dominated in stunted toddlers. Although the diversity indices showed no significant differences, unique bacterial genera were found in each toddler group: three genera unique to stunted toddlers and ten unique to healthy toddlers, with eight genera shared between the groups. We observed a higher number of enriched bacterial virulence genes in healthy vs. stunted toddlers suggesting that the microbiome plasticity and functional characteristics of the healthy toddlers allow for the pathogen/pathobiont control. In contrast, we noted the presence of more genes associated with antimicrobial-resistance (AMR) bacteria in stunted toddlers, possibly due to early-life antibiotic treatments. Of interest, functional analysis showed that CAZymes associated with carbohydrate biosynthesis, and a few metabolic pathways related to protein/amino acid, carbohydrate and fat catabolism were enriched in stunted toddlers. In contrast carbohydrate degradation CAZymes and numerous anabolic pathways were prevalent in healthy toddlers. These patterns were also evident in the Gn pigs transplanted with stunted/healthy human fecal microbiota (HFM). Overall, our findings suggest that the microbiota transplanted Gn pigs represent a valuable model for studying the infant microbial community structure and the impacts of stunting on the child gut microbiota. Additionally, this is the first study to demonstrate that the healthy vs. stunted microbiota composition and function remained different in the Gn pigs throughout the study. This information and the Gn pig model are vital for developing and testing targeted interventions for malnourished/stunted populations, consequently advancing microbiome-based diagnosis and personalized medicine.
由于缺乏用于研究发育迟缓病理生理学的可靠动物模型，我们对营养不良/发育迟缓与临床健康/正常的肯尼亚幼儿（12至24个月大）的肠道微生物群进行了比较表征，并建立了无菌猪粪便移植模型，以了解与发育迟缓相关的微生物群落结构。正如预期的那样，两组幼儿的细菌组成明显不同：放线菌在健康幼儿中最为普遍，而变形菌在发育迟缓幼儿中占主导地位。尽管多样性指数没有显著差异，但在每个幼儿组中都发现了独特的细菌属：发育迟缓幼儿中有三个独特的属，健康幼儿中有十个独特的属，两组之间共有八个属。我们观察到，与发育迟缓幼儿相比，健康幼儿中富集的细菌毒力基因数量更多，这表明健康幼儿的微生物群可塑性和功能特征有助于控制病原体/致病共生菌。相比之下，我们注意到发育迟缓幼儿中与抗菌药物耐药性（AMR）细菌相关的基因更多，这可能是由于早期使用抗生素治疗所致。有趣的是，功能分析表明，与碳水化合物生物合成相关的碳水化合物活性酶（CAZymes）以及一些与蛋白质/氨基酸、碳水化合物和脂肪分解代谢相关的代谢途径在发育迟缓幼儿中富集。相比之下，碳水化合物降解CAZymes和许多合成代谢途径在健康幼儿中普遍存在。这些模式在移植了发育迟缓/健康人类粪便微生物群（HFM）的无菌猪中也很明显。总体而言，我们的研究结果表明，移植了微生物群的无菌猪是研究婴儿微生物群落结构以及发育迟缓对儿童肠道微生物群影响的有价值模型。此外，这是第一项证明在整个研究过程中，无菌猪体内健康与发育迟缓微生物群的组成和功能仍然不同的研究。这些信息和无菌猪模型对于开发和测试针对营养不良/发育迟缓人群的靶向干预措施至关重要，从而推动基于微生物群的诊断和个性化医学的发展。
