Of all India’s stark health indicators, there were a couple that particularly puzzled Soumya Swaminathan, the former head of the Indian Council of Medical Research, including the country’s persistently high rates of anemia and wasting. Her search for an explanation led her to an unexpected place: the gut.

For Swaminathan, the first worrisome figures were those for anemia – nearly 53 percent of Indian women and 58 percent of children are anemic. Despite a large iron and folic acid supplementation and fortification program started by the government in 2012, the figures for women were unchanged. And children had registered only a marginal improvement in the decade between 2005 and 2015.

The second set of statistics concerned child malnutrition – where improvement varied between marginal and non-existent. The number of children classified as wasted had actually gone up from 19.8 percent to 21 percent in that same period.

Something was definitely amiss, but Swaminathan suspected the fault wasn’t entirely with the supplementation effort or other malnutrition programs. She remembers thinking that maybe it was time to look within at the microbiome – the millions of bacteria and viruses that live in the human body.

“We’d been looking at the microbiomes of malnourished people living in slums and found that their guts have large populations of pathogenic bacteria,” she said. “It seemed that these people were unable to absorb nutrients from the food and supplements, like iron, that they were getting.”

Focus on the microbiome is now at the cutting edge of scientific research on malnutrition. And while information is still scarce, there is emerging evidence that the microbiome dramatically affects nutritional status. That research has the potential to upend traditional interventions.

Exploring the Unknown

The human body is a complex ecosystem of thousands of genes and millions of cells. What has remained hidden from sight until very recently are the 100 trillion microorganisms that inhabit the human body, with the gut being the most densely populated.

This microcosm is poorly understood, though there is growing evidence that it plays a significant role in human health. The gut microbiome has been linked to everything from digestion to immunity.

Its connection to malnutrition was established in a series of studies on Malawian children starting in 2013. In one groundbreaking investigation that grew out of that work, a researcher considered the link between malnutrition and complex sugars found in breast milk. Mothers with stunted infants had low levels of these sugars. The researchers found that supplementing these sugars restored a balance in gut bacteria, leading to weight gain and pointing to a potential avenue for addressing malnutrition.

But microbiomes vary significantly across the world, largely due to differences in diet. Scientists would need to replicate this work in south Asia if they were to get to the bottom of India’s inability to combat anemia and malnutrition. Which they are now starting to do.

The Indian Microbiome

In 2014, researchers from the Center for Human Microbial Ecology at the Translational Health Science and Technology Institute published results after examining the gut microbiomes of 20 rural children of different nutritional levels. They found that malnutrition was linked with the presence of pathogenic bacteria, and the depletion of beneficial groups like Roseburia, which may help control inflammation.

In more targeted work published in 2016, another group of researchers compared the microbiomes of 10 children with low birth weight with 10 children of normal weight from a slum in south India, tracking them every three months until they turned two.

Their results showed the microbiota of children in the control group were rich in beneficial species. The guts of stunted children on the other hand, had high amounts of bacteria like Desulfovibrio and Campylobacterales, which are known to cause inflammation. In fact, these are the same bacteria that predominate in patients with inflammatory bowel diseases like ulcerative colitis.

One species, Bifidobacterium longum seemed to be particularly important, especially in the guts of healthy newborns, where it composed as much as 80 percent of their microbiome. Where it was present, there were few pathogenic bacteria, but its absence coincided with dysbiosis, a set of illnesses of the gastrointestinal tract that are linked to undernutrition. It is now at the center of microbiome-based research into countering child malnutrition in India.

Experts said there is still a significant amount of research that needs to be done to understand the link between these findings and forms of malnutrition like stunting. It is not even clear yet whether malnutrition leads to the proliferation of problematic bacteria ­– further exacerbating the problem – or if it is the other way around.

Scientists are focusing now on understanding basic patterns and correlations, and using the information they have, including the insights into the makeup of the healthy microbiomes, to pursue some potential interventions.

An Innovative Beginning

In Bangladesh, a study funded by the Bill and Melinda Gates Foundation is looking at using Bifidobacterium infantis – a subspecies of a bacteria known to help maintain a healthy digestive tract – to remedy the gut bacteria of severely malnourished children under six months old. These children were found to have almost no B. infantis in their guts.

One of the problems previous attempts to replenish bacteria through the use of probiotics have run into is the bacteria almost never seem to gain a lasting foothold in the gut.

But in research on breastfed babies in California, Evivo, an activated form of this bacteria manufactured by microbiome company Evolve BioSystems was found to persist in the guts of children as long as mothers were nursing their children. An initiative is underway to see if Evivo will be similarly persistent and effective in correcting dysbiosis in the very different set of children in Bangladesh.

Dr. Chris Damman of the Gates Foundation told News Deeply that they’re also funding OpenBiome, a non-profit stool bank “to evaluate replacing a more complex adult microbiome in the form of fecal microbial transplantation in older kids with malnutrition.”

The microbiome’s potential links to malnutrition also have nutrition experts reconsidering existing programs. It may be that for food and nutrient supplementation to be effective, it has to be accompanied by a more holistic approach that looks at minimizing exposure to pathogens and trying to restore balance in the microbiome.

In fact, recent work in Kenya has found current efforts may be doing more harm than good. A small amount of iron supplementation in Kenyan infants was found to significantly increase pathogenic bacteria and inflammation in the gut.

This could have serious ramifications in India and other places that have long been running iron and folic acid supplementation programs and may now need to reconsider those efforts.