Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition

Michael J. Barratt, Sharika Nuzhat, Kazi Ahsan, Steven A. Frese, Aleksandr A. Arzamasov, Shafiqul Alam Sarker, M. Munirul Islam, Parag Palit, Md Ridwan Islam, Matthew C. Hibberd, Swetha Nakshatri, Carrie A. Cowardin, Janaki L. Guruge, Alexandra E. Byrne, Siddarth Venkatesh, Vinaik Sundaresan, Bethany Henrick, Rebbeca M. Duar, Ryan D. Mitchell, Giorgio CasaburiJohann Prambs, Robin Flannery, Mustafa Mahfuz, Dmitry A. Rodionov, Andrei L. Osterman, David Kyle, Tahmeed Ahmed, Jeffrey I. Gordon

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition. Bifidobacterium longumsubspecies infantisis a prominent early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs). We found that the absolute abundance of Bifidobacteriuminfantisis 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-Nneotetraose 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.

Original languageEnglish
Article numbereabk1107
JournalScience translational medicine
Volume14
Issue number640
DOIs
StatePublished - Apr 13 2022

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