Human fecal transplantation from stunted children promotes metabolic dysfunction in mice fed with a high-fat and...

Stunting, or impaired child growth due to poor nutrition and infections, is characterized by a low height-for-age and affects 48%-56% of school-aged children worldwide. It is associated with later weight gain and chronic diseases. The gut microbiome in undernourished children may increase obesity risk if they are exposed to high-calorie environments. To investigate this, we assessed whether the intestinal microbiome of stunted children elevates obesity risk upon exposure to an obesogenic environment. Fecal microbiota transplantation (FMT) was performed using pooled stools from healthy (n = 6) or stunted (n = 6) school-aged children from a low-income cohort in Mexico. Eight-week-old male C57BL/6 mice underwent bowel cleansing with polyethylene glycol (PEG), followed by weekly intragastric FMT for 4 weeks. The mice were subsequently fed either a control diet (CT) or a high-fat, high-fructose corn syrup diet (HFFr, including 15% HFCS-55) for 15 weeks. Metabolic outcomes were assessed through body composition, indirect calorimetry, oral glucose tolerance test, insulin tolerance test, and histological analysis of visceral adipose tissue. The microbiota composition was evaluated by 16S rRNA V3-V4 hypervariable region sequencing, and the predicted functional capacity was analyzed using PICRUSt2. FMT from stunted children increased susceptibility to diet-induced obesity, visceral adipose tissue hypertrophy, and insulin resistance. In contrast, FMT from healthy children promoted energy expenditure and visceral adipose tissue hyperplasia, conferring a protective effect against diet-induced obesity and insulin resistance in the mice. Healthy-FMT led to sustained enrichment of Akkermansia and Parabacteroides, whereas stunting-FMT increased Proteobacteria, Veillonella, Desulfovibrionaceae, and Bifidobacterium. Microbial‒phenotypic correlations showed that Akkermansia and Parabacteroides were negatively correlated with fasting glucose, body weight, and fat mass, and positively correlated with postprandial RER, VO2, and lean mass. In conclusion, stunting-FMT recipient mice showed a higher risk of obesity and metabolic issues in an obesogenic environment. Healthy-FMT confers metabolic resilience, characterized by increased abundance of taxa such as Akkermansia and Parabacteroides, which are linked to enhanced energy expenditure, improved glucose metabolism, and favorable adipose tissue structure.