Malnutrition and dietary repair: Childhood malnutrition is accompanied by growth stunting and immaturity of the gut microbiota. Even after therapeutic intervention with standard commercial complementary foods, children may fail to thrive. Gehrig et al. and Raman et al. monitored metabolic parameters in healthy Bangladeshi children and those recovering from severe acute malnutrition. The authors investigated the interactions between therapeutic diet, microbiota development, and growth recovery. Diets were then designed using pig and mouse models to nudge the microbiota into a mature post-weaning state that might be expected to support the growth of a child. These were first tested in mice inoculated with age-characteristic gut microbiota. The designed diets entrained maturation of the children's microbiota and put their metabolic and growth profiles on a healthier trajectory. Science , this issue p. eaau4732 , p. eaau4735

Vitamin and mineral (micronutrient) deficiencies afflict 2 billion people. Although the impact of these imbalances on host biology has been studied extensively, much less is known about their effects on the gut microbiota of developing or adult humans. Therefore, we established a community of cultured, sequenced human gut–derived bacterial species in gnotobiotic mice and fed the animals a defined micronutrient-sufficient diet, followed by a derivative diet devoid of vitamin A, folate, iron, or zinc, followed by return to the sufficient diet. Acute vitamin A deficiency had the largest effect on bacterial community structure and metatranscriptome, with Bacteroides vulgatus, a prominent responder, increasing its abundance in the absence of vitamin A. Applying retinol selection to a library of 30,300 B. vulgatus transposon mutants revealed that disruption of acrR abrogated retinol sensitivity. Genetic complementation studies, microbial RNA sequencing, and transcription factor–binding assays disclosed that AcrR is a repressor of an adjacent AcrAB-TolC efflux system. Retinol efflux measurements in wild-type and acrR-mutant strains plus treatment with a pharmacologic inhibitor of the efflux system revealed that AcrAB-TolC is a determinant of retinol and bile acid sensitivity in B. vulgatus. Acute vitamin A deficiency was associated with altered bile acid metabolism in vivo, raising the possibility that retinol, bile acid metabolites, and AcrAB-TolC interact to influence the fitness of B. vulgatus and perhaps other microbiota members. This type of preclinical model can help to develop mechanistic insights about the effects of, and more effective treatment strategies for micronutrient deficiencies.

Malnutrition and dietary repair: Childhood malnutrition is accompanied by growth stunting and immaturity of the gut microbiota. Even after therapeutic intervention with standard commercial complementary foods, children may fail to thrive. Gehrig et al. and Raman et al. monitored metabolic parameters in healthy Bangladeshi children and those recovering from severe acute malnutrition. The authors investigated the interactions between therapeutic diet, microbiota development, and growth recovery. Diets were then designed using pig and mouse models to nudge the microbiota into a mature post-weaning state that might be expected to support the growth of a child. These were first tested in mice inoculated with age-characteristic gut microbiota. The designed diets entrained maturation of the children's microbiota and put their metabolic and growth profiles on a healthier trajectory. Science , this issue p. eaau4732 , p. eaau4735

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longum subspecies infantis is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacterium infantis is lower in 3- to 24-month-old Bangladeshi infants with severe acute malnutrition (SAM) compared to their healthy age-matched counterparts. A single-blind, placebo-controlled trial (SYNERGIE) was conducted in 2- to 6-month-old Bangladeshi infants with SAM. A commercial U.S. donor–derived B. infantis strain (EVC001) was administered daily with or without the HMO lacto- N -neotetraose for 28 days. This intervention increased fecal B. infantis abundance in infants with SAM, although to levels still 10- to 100-fold lower than in untreated healthy controls. EVC001 treatment promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM. We cultured fecal B. infantis strains from Bangladeshi infants and colonized gnotobiotic mice with these cultured strains. The gnotobiotic mice were fed a diet representative of that consumed by 6-month-old Bangladeshi infants, with or without HMO supplementation. One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N -glycans and plant-derived polysaccharides, exhibited superior fitness over EVC001. The fitness advantage of Bg_2D9 was confirmed in a gnotobiotic mouse model of mother-to-infant gut microbiota transmission where dams received a pretreatment fecal community from a SAM infant in the SYNERGIE trial. Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing.