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

  • 2022-04-13
  • Science Translational Medicine 14(640)
    • Michael J. Barratt
    • Sharika Nuzhat
    • Kazi Ahsan
    • S. Frese
    • Aleksandr A. Arzamasov
    • S. Sarker
    • M. M. Islam
    • P. Palit
    • Md. Ridwan Islam
    • M. Hibberd
    • Swetha Nakshatri
    • Carrie A. Cowardin
    • J. Guruge
    • A. Byrne
    • Siddarth Venkatesh
    • Vinaik Sundaresan
    • B. Henrick
    • R. Duar
    • Ryan D. Mitchell
    • G. Casaburi
    • Johann Prambs
    • Robin L. Flannery
    • M. Mahfuz
    • D. Rodionov
    • A. Osterman
    • David Kyle
    • T. Ahmed
    • J. Gordon

Abstract

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.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
BifidobacteriumIncreased Bifidobacterium AbundanceBeneficial
Moderate
BifidobacteriumPromoted Weight GainBeneficial
Moderate
BifidobacteriumReduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantisIncreased Body WeightBeneficial
Moderate
Bifidobacterium infantisReduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantis BI02Increased Body WeightBeneficial
Moderate
Bifidobacterium infantis BI02Reduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantis Bi-26Increased Bifidobacterium AbundanceBeneficial
Moderate
Bifidobacterium infantis Bi-26Promoted Weight GainBeneficial
Moderate
Bifidobacterium infantis Bi-26Reduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantis HA-116Promoted Weight GainBeneficial
Moderate
Bifidobacterium infantis HA-116Reduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantis M-63Promoted Weight GainBeneficial
Moderate
Bifidobacterium infantis MAK22B041Promoted Weight GainBeneficial
Moderate
Bifidobacterium infantis MAK22B04IIncreased Body WeightBeneficial
Moderate
Bifidobacterium infantis MAK22B04IReduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantis SD-6720Promoted Weight GainBeneficial
Moderate
Bifidobacterium infantis SD-6720Reduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium infantis VPro 53Increased Body WeightBeneficial
Moderate
Bifidobacterium infantis VPro 53Reduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium longum MM-2Promoted Weight GainBeneficial
Moderate
Bifidobacterium longum MM-2Reduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium longum subsp. infantisPromoted Weight GainBeneficial
Moderate
Bifidobacterium longum subsp. infantisReduced Intestinal InflammationBeneficial
Moderate
Bifidobacterium longum subsp. infantis M-63Promoted Weight GainBeneficial
Moderate
Bifidobacterium longum subsp. infantis M-63Reduced Intestinal InflammationBeneficial
Moderate
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