Data published in Science Translational Medicine indicated that while Bifidobacterium longum subspecies infantis EVC001 (Evolve Biosystems) produced significant improvements in Bangladeshi infants with sever acute malnutrition (SAM), the strain, which is derived from a US infant donor, the level of colonization was lower than B. infantis levels recorded in health Bangladeshi infants.
This led the researchers to look for a B. infantis strains with greater colonization. Strains were cultured from the local population in Bangladesh and identified one strain designated Bg_2D9 that not only utilized complex carbohydrates in the local trial better than EVC001 but was also a better colonizer of the infant gut.
“Bacterial strain selection is a critical element in designing future therapies for repairing dysfunctional gut microbial communities that lead to malnutrition,” co-senior author Jeffrey Gordon, MD, director of the Edison Family Center for Genome Sciences and Systems Biology at Washington University School of Medicine, told WUSTL’s The Source.
“This pilot study not only shows promising results in treating children with severe acute malnutrition but also underscores how proper development of the gut microbiota is linked to healthy growth of infants.”
The WUSTL researchers, working with International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh conducted the SYNERGIE study, a single-blind, placebo-controlled trial with 60 Bangladeshi infants with SAM aged between two and six months. The infants, all of whom received a standard-of-care diet, were randomly assigned to one of three groups: B. infantis EVC001; B. infantis EVC001 plus the HMO lacto-N-neotetraose; or placebo for four weeks.
Results showed that the infants receiving the probiotic experienced greater weight gain and led intestinal inflammation, but B. infantis levels were significantly lower in the SAM infants compared to healthy control infants.
“At the start of the trial, B. infantis — this very important early colonizer of the infant gut — was either completely absent or present at only very low levels in infants with severe acute malnutrition,” first author Michael Barratt, PhD, from Washington University told WUSTL’s The Source.
“While the interventions increased the representation of B. infantis, the levels observed were still well below those we see in healthy breastfed infants of the same age in this Bangladeshi community. The results are very encouraging but left a question in our mind: Can we do even better?”
This led them to screen B. infantis strains isolated from Bangladeshi infants, and the discovery of Bg_2D9, which was found to express two gene clusters involved in uptake and utilization of plant-derived carbohydrates present in the local diet.
Next, the Bg_2D9 strain was tested in lab mice – specifically germ-free mice that had their gut colonized by the microbiome of an infant with SAM. This data showed that Bg_2D9 was indeed a more efficient colonizer than the EVC001 strain in mice, an observation that now needs to be explored in trials involving malnourished infants.
“Given the unique genomic features of the Bangladeshi B. infantis strain that confer superior fitness in our preclinical models, we now plan to repeat the human study using this strain,” said Barratt. “This will allow us to determine whether the results translate to infants with severe acute malnutrition in Bangladesh through improved growth and more durable recovery from severe malnutrition.”
Source: Science Translational Medicine
Vol 14, Issue 640, doi: 10.1126/scitranslmed.abk1107
“Bifidobacterium infantis treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition”
Authors: M.J. Barratt et al.