LAUSR

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. Description Restoring Bifidobacterium infantis to the gut of malnourished infants boosts weight gain and reduces inflammatory markers. Fighting malnourishment with probiotics Bifidobacterium infantis, a gut bacterium uniquely adapted to metabolizing breastmilk carbohydrates, is deficient in Bangladeshi infants with severe acute malnutrition (SAM). A U.S. donor–derived B. infantis strain improved weight gain and reduced intestinal inflammation in infants with SAM. A strain cultured from a healthy Bangladeshi child with expanded capacity to metabolize both plant and milk carbohydrates achieved greater colonization and augmented weight gain in gnotobiotic mice colonized with a fecal microbial community from an infant with SAM. This probiotic strain may help to treat acutely malnourished infants, especially those who have a breastmilk-poor diet.