<i>Bifidobacterium infantis</i> treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition

<jats:p> Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. <jats:italic>Bifidobacterium longum</jats:italic> subspecies <jats:italic>infantis</jats:italic> is a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of <jats:italic>Bifidobacterium infantis</jats:italic> 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 <jats:italic>B. infantis</jats:italic> strain (EVC001) was administered daily with or without the HMO lacto- <jats:italic>N</jats:italic> -neotetraose for 28 days. This intervention increased fecal <jats:italic>B. infantis</jats:italic> 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 <jats:italic>B. infantis</jats:italic> 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 <jats:italic>B. infantis</jats:italic> strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of <jats:italic>N</jats:italic> -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. </jats:p>