Probiotics Combat Infant Malnutrition by Restoring Key Gut Bacteria

By Marilynn Larkin

April 20, 2022

NEW YORK (Reuters Health) - In severely malnourished Bangladeshi infants, restoring a strain of the bacterial species Bifidobacterium infantis promoted rapid weight gain and lowered markers of intestinal inflammation, researchers say.

B. infantis is an early colonizer of the infant gut that consumes human milk oligosaccharides (HMOs).

"The gut microbiota of children with severe acute malnutrition (SAM) exhibited a profoundly different microbiota composition than that of healthy age-matched infants living in the same community," Dr. Michael Barratt of Washington University School of Medicine in St. Louis told Reuters Health by email.

"The SAM microbiota was less mature and lacked important members of the healthy gut microbiota, notably (B. infantis)," he said. "Instead, it was dominated by bacterial species that have the potential to have adverse effects on the child, including causing intestinal inflammation, disrupting gut barrier function, and interfering with nutrient absorption."

"Treatment of infants with SAM with a commercial probiotic strain isolated from a US infant provided partial restoration of B. infantis levels, though still to levels well below those found in healthy children," he noted. "The treatment improved weight gain and this was associated with improvements in biomarkers of intestinal inflammation."

"Surprisingly," he added, "animal studies of B. infantis strains isolated from healthy Bangladeshi children identified a strain that had unique genomic features that enabled it to be more competitive - i.e., exhibit more robust gut colonization - than the strain used in our clinical trial, in a realistic Bangladeshi diet containing milk plus plant-based ingredients."

As reported in Science Translational Medicine, Dr. Barratt and colleagues conducted a single-blind, placebo-controlled trial (SYNERGIE) in 62 Bangladeshi infants (2- to 6-months-old) with SAM. They gave the infants a commercial strain of B. infantis, EVC001, derived from a US infant donor.

EVC001 was given daily with or without the HMO lacto-N-neotetraose supplementation for 28 days. As Dr. Barratt indicated, the intervention increased fecal B. infantis abundance in infants with SAM, although to levels 10- to 100-fold lower than in untreated controls without SAM. EVC001 also promoted weight gain that was associated with reduced intestinal inflammation markers in infants with SAM.

The team then cultured fecal B. infantis strains from healthy Bangladeshi infants and colonized gnotobiotic mice with the cultured strains. The mice were fed a diet similar to that consumed by 6-month-old Bangladeshi infants, with or without HMO.

One B. infantis strain, Bg_2D9, expressing two gene clusters involved in uptake and utilization of N-glycans and plant-derived polysaccharides, showed a greater capacity to break down the plant sugar and carbohydrates and led to more weight gain compared with EVC001 in two mouse models.

The authors note, "Whether Bg_2D9 is superior to EVC001 for treating malnourished infants who consume a diet with limited breastmilk requires further clinical testing."

Dr. Barratt added, "While very promising, our small pilot study was principally designed to measure efficiency of colonization of the B. infantis strain. Larger studies are required to confirm the safety of the intervention in these vulnerable children, and to establish robust data about the magnitude and durability of the clinical benefit, including identifying the optimal duration and frequency of dosing."

"Moreover," he said, "... the degree to which B. infantis deficiency is a hallmark of SAM in other settings would first need to be established."

Dr. Rebecca Knickmeyer, Associate Professor in the College of Human Medicine's Department of Pediatrics and Human Development at Michigan State University in East Lansing called the study "very promising."

However, she said, "While the focus on B. infantis is well justified, it is important to note that Bifidobacterium species represent a relatively small percentage of the overall microbial community in many infants - other members may also have potentially beneficial effects or detrimental effects relevant to SAM."

"Infants with SAM were dominated by pathobionts including Escherichia, Shigella, Klebsiella, and Streptococcus, but treatment with EVC001 did not significantly reduce the relative abundance of these taxa," she noted. "The mouse studies suggest that Bg_2D9 might perform better in this regard."

"Also, levels of EVC001 dropped substantially after treatment ceased and treatment didn't seem to affect the overall composition of the microbiome," she said. "In other words, treatment didn't induce long-lasting changes."

"The maternal-infant studies in mice suggest that maternal probiotic treatments during pregnancy could help prevent SAM," she added. "I thought that was very exciting, as treatment of children who are already ill is unlikely to fully reverse negative developmental consequences of SAM, including neurodevelopmental ones."

SOURCE: Science Translational Medicine, online April 13, 2022.