The research findings, published as two separate papers in Science, indicate that healthy development of the gut microbial community following birth is crucial for the overall growth and development of infants.

The study was led by Dr. Tahmeed Ahmed, MBBS, Ph.D, who is the Senior Director of the Nutrition and Clinical Services Division at ICDD R, B.

The senior author was Dr. Jeffrey I. Gordon, MD, who is the Dr. Robert J. Glaser Distinguished University Professor in the Department of Pathology & Immunology and Director of the Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine in St. Louis, Missouri, USA.

Childhood Malnutrition and Limitations of Conventional Therapeutic Foods

Childhood malnutrition is a huge global problem that is characterized by stunting, wasting, underweight, and failure to thrive. As per UNICEF/WHO/World Bank Joint Child Malnutrition Estimates (March 2019), currently, there are 149 million stunted and 49 million wasted children under the age of 5 years worldwide.

Malnutrition is associated with an increased risk of infections, as well as impaired cognitive ability, leading to poor school performance. Malnutrition is caused by many factors, the major being the inaccessibility to adequate amounts of affordable and nutritious food.

Conventional therapeutic foods for children are designed to increase the nutrients that are normally utilized by the body. However, these are largely ineffective in malnourished children suffering from stunting, reduced immunity and impaired cognitive abilities. Gordon believes that the underlying reason is that these therapeutic foods were not designed for promoting the healthy development of the gut microbiome.

Development of Microbiota Directed Complementary Food (MDCF)

The new Microbiota Directed Complementary Food (MDCF), which has been jointly developed by the Washington University School of Medicine in St. Louis and ICDDR, B, was based on their previous collaborative studies in healthy and malnourished children in Bangladesh. When they compared the gut microbiota of healthy and malnourished children, they were surprised to find that the bacterial flora in the gut of malnourished children was much more immature than that of their age-matched healthy counterparts. Moreover, conventional therapeutic foods were unable to repair the immature gut microbiota in malnourished children. This led the researchers to focus on developing a new type of designer therapeutic food, which resulted in MDCF.

"We found that children who are malnourished have incompletely formed gut microbial communities compared with their healthy counterparts," says Gordon."Therefore, we set about to design therapeutic foods to repair this immaturity and to determine whether such repair would restore healthy growth."

Mice Studies

Immature gut microbiota taken from malnourished children and healthy gut microbiota taken from healthy children were transplanted into mice that were maintained under sterile conditions.

Mice transplanted with immature microbiota became underweight, developed defective bones, as well as abnormalities in immune and metabolic functions. This provided vital evidence that failure to form a healthy microbiota could actually be the cause, rather than the effect of malnutrition.

Human Studies

A clinical trial was conducted on Bangladeshi children, which had the following key features:

• The clinical trial was conducted over a period of one month
• The sample size was 63
• The children were aged between 12-18 months
• The children were diagnosed with moderate acute malnutrition
• There were four treatment groups
• Children were randomly assigned to one of the four groups
• Children in three of the treatment groups received one of the newly designed MDCF
• Children in the fourth group received conventional therapeutic food
• Food for the clinical trial was produced at ICDDR, B
• Food was administered twice a day by the mothers under the supervision of health workers
• Genomic analysis was carried out on the gut microbiota of the treated children
• This enabled identification of the molecular features of malnutrition, its mechanism of development, and efficacy of treatment
• 1,300 blood proteins were analyzed that influenced the following parameters:
• Bone growth
• Brain development
• Immune functions
• Metabolic functions
• One MDCF was superior to the others, due to its positive influence on the above parameters, shifting them towards a healthy state
• The condition of the gut microbiota of children receiving the above lead therapeutic MDCF improved significantly and resembled that of healthy children
• The formula of the lead therapeutic MDCF included extracts from bananas, soy, chickpeas, and peanuts

"There is uncertainty about what foods are best to administer during the period of complementary feeding - when children transition from exclusive milk feeding to solid foods," says Gordon. "Our studies were inspired by the notion that these commonly used, affordable, culturally acceptable complementary foods could contain ingredients coveted by key microbes that are underrepresented and underperforming in the gut microbiomes of malnourished children. These microbes were our therapeutic targets."

Importance of the Study

The importance of the study stems from the fact that it provides the first evidence of a therapeutic food, solely designed for improving the gut microbiota, also provides beneficial effects outside the gut. These include positive influences on healthy bone and brain development, as well as improvement of immune and metabolic functions. Importantly, these organ systems can't be repaired in malnourished children with conventional a therapeutic foods.

Future Plans

The research team plans to evaluate the newly developed MDCF in longer and larger clinical trials in Bangladesh to establish whether it has any sustained benefits. The trials will include children with moderate to severe malnutrition, treated with conventional therapy, but with impaired microbiomes, stunting and other growth abnormalities.

The research team also plans to explore whether specific beneficial microbes or products made by them can be co-administered with MDCF to children with severely damaged gut microbiomes, which can't be repaired by food-based interventions alone.

They also plan to monitor the developing gut microbial flora in infants, so that any deviations from the normal pattern can be detected earlier in life, offering an opportunity for prevention.

Concluding Remarks

Gordon stressed that the new therapeutic food that they have developed for repairing the damaged gut microbiomes of infants and children, could help develop better dietary guidelines for feeding them in their first few years of life so that they can develop healthy gut microbiomes.

"We need to be effective stewards of the precious microbial resources of our children," he said. "If we are, the effects may be long-lived and herald a new dimension to preventive medicine - one that starts with their developing microbiomes."

Funding Source

The study was funded by the National Institutes of Health, Bill & Melinda Gates Foundation, Washington University School of Medicine, Agilent Technologies, and the Russian Science Foundation.

References :

1. Effects of Microbiota-directed Foods in Gnotobiotic Animals and Undernourished Children - (https://science.sciencemag.org/content/365/6449/eaau4732)
2. A Sparse Covarying Unit that Describes Healthy and Impaired Human Gut Microbiota Development - (https://science.sciencemag.org/content/365/6449/eaau4735)

Source: Medindia