The study was jointly
conducted by the Washington University School of Medicine in St. Louis and the
International Center for Diarrheal Disease Research, Bangladesh (ICDDR, B).
The research team used a new strategy that
selectively boosts only those gut bacteria
that have growth-promoting properties.
The therapeutic food was developed using ingredients that are locally
available, affordable accessible, and culturally acceptable.
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
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
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
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
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.
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
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
says Gordon."Therefore, we set about to design
therapeutic foods to repair this immaturity and to determine whether such
repair would restore healthy growth."
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.
A clinical trial
was conducted on Bangladeshi children, which had the following key features:
"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,"
- The clinical trial was conducted over a period of
- The sample size was 63
- The children were aged between 12-18 months
- The children were diagnosed with moderate acute
- There were four treatment groups
- Children were randomly assigned to one of the four
- Children in three of the treatment groups received
one of the newly designed MDCF
- Children in the fourth group received conventional
- 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
- 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
- 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
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.
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
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.
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
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
- Effects of Microbiota-directed Foods in Gnotobiotic Animals and Undernourished Children - (https://science.sciencemag.org/content/365/6449/eaau4732)
- A Sparse Covarying Unit that Describes Healthy and Impaired Human Gut Microbiota Development - (https://science.sciencemag.org/content/365/6449/eaau4735)