microbiome Archives - Sanford Burnham Prebys
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Common gut bacteria have a taste for tungsten

AuthorGreg Calhoun
Date

January 9, 2025

A bacteria linked to longevity was found to feast on lactate only when the meal contains the metallic side dish

In a new paper published December 30, 2024, in PNAS, study coauthor Dmitry A. Rodionov, PhD, research assistant professor in the Immunity and Pathogenesis Program at Sanford Burnham Prebys, and colleagues, studied how Eubacterium limosum contribute to a healthy human gastrointestinal microbiome by metabolizing lactate.

Lactate or lactic acid is a normal byproduct that is created as our cells generate energy. Lactate can be found in the guts of healthy adults at low concentrations because microbes such as E. limosum make a meal of much of it, preventing the abnormal accumulation sometimes found in patients suffering from ulcerative colitis and other gut-related disorders.

Rodionov and his colleagues examined how E. limosum bacteria break down lactate into short-chain fatty acids (SCFAs) and were surprised to find that the metabolic process depends on two tungsten-containing enzymes.

The authors suggest that their findings are a tipoff that tungsten might be an overlooked micronutrient in the human gut microbiome and may contribute in unappreciated ways to overall human health.

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Gut microbiome repair in children with severe acute malnutrition

AuthorScott LaFee
Date

October 2, 2024

Child malnutrition remains an alarming and appalling scourge.

In 2022, according to the World Health Organization, 148 million children in the world under 5 years were too short for their age (stunting) and another 45 million were too thin for their height (wasting) due to inadequate diet and nutrition.

Researchers around the world, including Andrei L. Osterman, PhD, professor in the Immunity and Pathogenesis Program at Sanford Burnham Prebys, have been investigating potential remedies, in particular some of the consequences of malnutrition, such as disturbed metabolism and immune/gut function.

In a new paper published October 2, 2024 in Science Translational Medicine, the multi-institutional team (including Osterman and colleagues at SBP) describe an interventional diet that essentially repairs the gut microbiome in children with moderate to severe acute malnutrition.

They conducted a three-month randomized controlled trial of a specialized food supplement in 12- to 18-month-old Bangladeshi children living in rural and urban slums with moderate acute malnutrition who had already been treated in hospital for severe acute malnutrition. The supplement, called microbiota-directed complementary food or MDCF-2, contains chickpea flour, peanut flour, soy flour, green banana, sugar, soybean oil and a vitamin-mineral premix, a formulation designed to promote the growth of therapeutic gut bacteria and improve the overall health and balance of the gut microbiome.

They found that MDCF-2 improved weight-for-age better than the traditional ready-to-use supplementary food (RUSF) used by relief agencies and others, which is composed of more traditional ingredients like rice, lentil, sugar, soybean oil and skimmed milk powder mixed with vitamins and minerals.

When excluding children unable to continue study participation due to severe flooding during the trial, the study authors also reported improvement of stunting at a faster rate. They tied these improvements in children’s health to Prevotella copri–associated metabolic changes.

P. copri (recently renamed as Segatella copri) is a bacterium found abundantly in the human gastrointestinal microbiome. Past studies have reported both positive and negative associations with health and disease. In the former, for example, healthy bacterial colonization of the gut has been positively correlated with conditions like inflammation, insulin resistance and diarrhea. It appears to be a major player in regulating dietary metabolism.

The bacterium is more common in non-Westernized populations consuming a diet rich in plants—the bacterium’s source of nutrients. In Western populations, it is associated with consumption of fruits and vegetables.

Genomic reconstruction of the metabolic potential of P. copri strains positively associated with infants’ health improvement confirmed their unique ability to utilize a large repertoire of plant-derived polysaccharides comprising MDCF-2 diet.

“This study can be viewed as a test of the generalizability of the efficacy and mechanism of action of MDCF-2 in acutely malnourished children,” said Osterman. “The main findings include the demonstration of significantly higher efficacy of MDCF-2 vs RUSF with respect to the improvement of (weight) growth.

“The success of the treatment was also manifest by beneficial changes in microbiome composition and by global changes of a range of serum protein biomarkers associated with healthy development.”

The findings, he said, also provide proof-of-concept that improving gut microbial health can be achieved using therapeutic nutrition and offers further guidance on how best to use microbiota-directed complementary foods.

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Sanford Burnham Prebys research plays a key role in developing microbiome-directed complementary food to help save malnourished children

AuthorScott LaFee
Date

January 4, 2024

Among the consequences of childhood malnutrition is the underdevelopment of their gut microbiomes, critical to human health, from innate immunity to appetite and energy metabolism.

Although malnourished children gain some weight and grow better when fed a nutrient-rich diet, they do not catch up to their well-fed counterparts—and their gut microbiomes do not recover.

In a 2021 clinical trial, researchers at Washington University School of Medicine showed how a newly designed therapeutic food—a unique mix of peanuts, bananas and other foods dubbed microbiome-directed complementary food, or MDCF—more effectively nourished healthy gut microbial communities than standard dietary supplements.

Now, with bioinformatics support from Andrei L. Osterman, PhD, professor in the Immunity and Pathogenesis and Cancer Metabolism and Microenvironment programs at Sanford Burnham Prebys  and his colleagues Dmitry Rodionov, PhD, and Alex Arzamasov, the multi-institutional scientific team has published new research that identifies and describes the bioactive elements of microbiome-directed food.

“These are naturally occurring carbohydrate structures that could, in theory, be recovered in large quantities from the by-product streams of food manufacturing and be used to produce prebiotics,” said senior study author Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor at Washington University.

“We also have identified the microbes that process these food components, and in theory, there is potential for the organisms themselves to be part of a therapeutic intervention in children completely lacking these beneficial gut microbes.”

Osterman’s lab contributed bioinformatics analyses of 1,000 new metagenomically assembled genomes, or MAGs, representing the gut microbiomes of healthy Bangladeshi infants. The analyses included genome-based inference of the presence or absence in these MAGs of functional metabolic pathways for 106 major nutrients and intermediary metabolites.

“These predictions enabled the assessment of the microbiome-wide representation or enrichment of dietary carbohydrate utilization capabilities across numerous biospecimens from a randomized, controlled trial of MDCF in Bangladeshi children with moderate acute malnutrition,” said Osterman.

“The analyses helped elucidate glycan components of MDCF metabolized by bacterial taxa that are positively associated with healthy weight growth. The knowledge will help guide the therapeutic use of current MDCF and enable development of new formulations.”

Childhood undernutrition is a global scourge. In 2020, an estimated 149 million children under the age of 5 had stunted growth (low height for age), and 45 million exhibited stunting (low weight for height). More than 30 million children worldwide have moderate, acute malnutrition.

Undernutrition and its consequences are the leading causes of disease and death for children in this age range. An estimated 3 million children die each year due to poor nutrition and hunger.

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How our immune system controls gut microbes

AuthorMiles Martin
Date

April 6, 2022

And how this relationship could help fight autoimmune diseases

Sanford Burnham Prebys researchers including Carl Ware, PhD, and John Šedý, PhD have discovered an immunological process in the gut that could help improve treatment for autoimmune and gastrointestinal diseases. The study, published March 22 in Cell Reports, found that this process regulates the activation of white blood cells in the intestines, which ultimately helps the body control the composition of the gut microbiome. 

“The immune system is like a gardener for our gut bacteria, gently monitoring and responding to their populations and keeping an eye out for unwanted pathogens” says Ware, who directs the Infectious and Inflammatory Diseases Center at Sanford Burnham Prebys. “This ultimately helps the immune system control these microbes.”

This “gardening” relies on a molecule called BTLA, one of several checkpoint proteins used by the body to control the immune system. 

“This is a signaling system we’ve known about for decades, but this is a totally new function for it that we’ve never seen before,” says Šedý, a Sanford Burnham Prebys research assistant professor, who co-led the study with Ware. “I helped discover this system two decades ago, so it’s exciting that we’re still making new discoveries about its function.”  

To explore the role of BTLA in the gut, the team zeroed in on specialized lymph nodes in the intestines called Peyer’s patches, which are full of white blood cells that help monitor and respond to pathogens and other microbes in the gut.

“Gut bacteria are in constant competition, and the populations of specific species can fluctuate,” says Ware. “In a healthy microbiome, there’s a balance, and disrupting that balance can contribute to autoimmune diseases, gastrointestinal disorders and even some brain disorders.”

The team found that BTLA is critical for maintaining this balance because it triggers white blood cells to release antibodies that control the populations of different gut bacteria.

“It’s a finely calibrated system that we’re still only just beginning to understand in detail,” adds Ware.

Immune checkpoints like BTLA are already used in immunotherapy for some cancers, and these results make the researchers confident that this system can be leveraged to treat diseases in the gut, especially those that are also autoimmune disorders, such as Crohn’s disease or ulcerative colitis. 

“The immune system is unimaginably complex, and understanding it gives us the ability to manipulate it, and that can help us treat diseases,” says Šedý. “This discovery is a step forward in that larger narrative.” 

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How microbes shape human health: an interview with Andrei Osterman

AuthorMiles Martin
Date

October 7, 2021

In his work on the human microbiome, Sanford Burnham Prebys professor Andrei Osterman, PhD, has shown how the organisms living within us can be leveraged to boost human health for a humanitarian cause – the plight of malnourished children. 

Describe your research aimed to improve the gut microbiome in malnourished children.
In infants, it’s been well-established that conditions of severe poverty and food insecurity cause a delayed development of gut microbes, and that this results in stunted growth, numerous syndromes, and even death. My team has been collaborating with researchers at Washington University in St. Louis to develop foods that are designed to enhance the microbiome, and we’ve found that these can actually work to correct some of these pathologies. 

One study involved introducing microbes from undernourished Bangladeshi children into the guts of mice. When these mice were then fed a typical Bangladeshi diet, they exhibited a weaker immune response to the oral cholera vaccine. More importantly, this poor response could be repaired by establishing a more normal gut microbiome in the mice and providing them supplements to boost these microbes’ propagation.

What else can we learn from this research that could be applied more broadly?
From a humanitarian perspective, the progress we’ve made is so valuable that there is no question we will continue the work. But studying the microbiome in infants, regardless of their food security, can also provide us with new insights into the importance of the microbiome in human health. 

In a more recent study with collaborators from University of California San Diego and University of Southern California, we found that adding corn syrup to infant formula can enhance the populations of beneficial microbes they might otherwise have gotten from breast milk. 

We hope this is the first of many studies we work on with this team, because the transition of infants from breast milk or formula to conventional foods is thought to be the most drastic example of how the microbiome changes with diet. Studying infants and their diets at this early point in life could help reveal fundamental truths that we’ll be able to translate to other syndromes related to the microbiome in children and adults worldwide, regardless of food security. 

And this isn’t just speculation. Another study with the team in St. Louis used the same methods as the malnutrition study to develop supplementary foods, called “fiber snacks,” to correct microbiome imbalances in people with obesity. One might think that obesity would be the total opposite of malnutrition, but the microbiome is a key player in both. 

More broadly, gut microbes are already the most well-studied part of the human microbiome, and the list of health associations with these microbes extend well beyond the digestive tract, even into the immune system, affecting the risk for diseases like cancer or diabetes. There’s also a growing body of evidence that suggests that gut microbes can have a direct effect on the brain. For example, the microbiome is being studied closely in connection to autism spectrum disorder, since many people on the spectrum experience concurrent gastrointestinal syndromes.

What would you say is important to know for people not familiar with the subject?
We need to acknowledge that our body and many of its problems have a huge microbiome component. The human body is a complex organism, and we are still learning how the microbiome influences and is influenced by different health conditions. The next step is to incorporate the role of the microbiome into the design of new diagnostics and therapeutics—because this undoubtedly influences their effectiveness. We can’t ignore this aspect of our biology, and the time is ripe to improve our understanding of it and leverage it to our advantage. Moving forward, this is going to help us solve so many problems—from issues we’ve already started looking at like obesity and malnutrition, all the way through to problems we aren’t even aware of yet. 

What are the next steps for you and your team?
What we’re really interested in now is exploring new genomic technologies that are starting to revolutionize the field. The latest development is something called MAG genomics, short for metagenomically assembled genomes. This involves looking at the big picture, sequencing DNA from the whole microbiome at once in a way that is much faster and of much better quality than we’ve ever been capable of before. It’s like the difference between watching a movie on a clunky pixelated monitor from the 80’s and seeing that same movie on an HD monitor. Methods like this are moving us into a new paradigm in biomedical research, one that may be more complex, but also one that has the potential to substantially improve health outcomes for people around the world.

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A year in review: Our top 10 discoveries of 2019

AuthorMonica May
Date

December 4, 2019

At Sanford Burnham Prebys, we uncover the origins of disease and launch bold new strategies that lay the foundation for achieving cures. This year our scientists made significant progress—revealing new insights into how we treat some of the deadliest cancers, address neurological disorders such as Parkinson’s and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and more.

Read on to learn more about our top 10 discoveries of the year. To receive more frequent updates on our discoveries, subscribe to our monthly newsletter at the bottom of this page.

  1. One-two punch drug combination offers hope for pancreatic cancer therapy. Ze’ev Ronai, PhD, identified a combination of two anti-cancer compounds that shrank pancreatic tumors in mice—supporting the immediate evaluation of the drugs in a clinical trial. The study was published in Nature Cell Biology.
  2. Targeted treatment shrinks deadly pediatric brain tumors. Robert Wechsler-Reya, PhD, reported that a targeted therapy that blocks a protein called LSD1 shrank tumors in mice with a form of pediatric brain cancer known as medulloblastoma. LSD1 inhibitors are currently under evaluation in clinical trials for other cancers, which could speed their potential path to children. The study was published in Nature Communications.
  3. Epigenetic change causes fruit fly babies to inherit diet-induced heart disease. Rolf Bodmer, PhD, showed that reversing an epigenetic modification or over-expressing two genes protected fruit fly children and grandchildren from the negative heart effects of their parents’ fatty diet. These findings help explain how obesity-related heart failure is inherited and uncover potential targets for treatment. The study was published in Nature Communications.
  4. Amyotrophic lateral sclerosis (ALS) research reveals new treatment approach. Huaxi Xu, PhD, extended the survival of mice with ALS-like symptoms by elevating levels of a protein called membralin using a gene therapy approach. The study was published in the Journal of Clinical Investigations.
  5. How prostate cancer becomes treatment resistant. Jorge Moscat, PhD, and Maria Diaz-Meco, PhD, identified how prostate cancer transforms into an aggressive, treatment-resistant subtype called neuroendocrine prostate cancer (NEPC) following treatment with anti-androgen therapy. Their findings uncover new therapeutic avenues that could prevent this transformation from occurring and reveal that an FDA-approved drug holds promise as an NEPC treatment. The study was published in Cancer Cell.
  6. Boosting muscle stem cells to treat muscular dystrophy and aging muscles. Alessandra Sacco, PhD, uncovered a molecular signaling pathway that regulates how muscle stem cells decide whether to self-renew or differentiate—an insight that could lead to muscle-boosting therapeutics for muscular dystrophies or age-related muscle decline. The study was published in Nature Communications.
  7. Functional hair follicles grown from stem cells. Alexey Terskikh, PhD, created natural-looking hair that grows through the skin using human induced pluripotent stem cells (iPSCs), a major scientific achievement that could revolutionize the hair growth industry. Stemson Therapeutics has licensed the technology.
  8. Potential targeted treatment for acute myeloid leukemia identified. Ani Deshpande, PhD, showed that a protein called BMI1 is a promising drug target for an AML subtype in which two normally separate genes fuse together. The findings, published in Experimental Hematology, provide a rationale for evaluating a BMl1-inhibiting drug that is currently in clinical development as a potential treatment for this subtype.
  9. Antimicrobial protein implicated in Parkinson’s disease. An immune system protein that usually protects the body from pathogens is abnormally produced in the brain during Parkinson’s disease, Wanda Reynolds, PhD, reported in Free Radical Biology & Medicine. The discovery indicates that developing a drug that blocks this protein, called myeloperoxidase (MPO), may help people with Parkinson’s disease.
  10. Digestion-aiding herbs alter gut microbiome. Scott Peterson, PhD, found that four herbs—turmeric, ginger, long pepper and black pepper—promoted strong shifts in the gut bacteria that are known to regulate metabolism, providing insights that could help us protect our health. The study was published in Evidence-Based Complementary and Alternative Medicine.
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Digestion-aiding herbs alter gut microbiome

AuthorMonica May
Date

July 24, 2019

Many medicines used today—including aspirin, penicillin and malaria-fighting quinine—originated from nature. Now, Sanford Burnham Prebys and UC San Diego scientists have turned to ancient digestive herbs to learn about gut health—in the hopes of uncovering new treatments for colon cancer, autoimmune conditions and additional serious diseases.

In a recent study published in Evidence-Based Complementary and Alternative Medicine, the researchers examined how four herbs—turmeric, ginger, long pepper and black pepper—change the gut microbiome. These herbs have been used for more than 5,000 years to aid digestion in Ayurvedic healing, India’s traditional system of medicine. The researchers found that the herbs promoted strong shifts in the gut bacteria that are known to regulate metabolism—providing insights that could help us protect our health. 

“Scientists have long known that these four herbs facilitate digestion and increase bioabsorption of dietary nutrients. However, the effects on the gut microbiome had not been studied,” says Scott Peterson, PhD, senior author of the paper and a professor at Sanford Burnham Prebys. “Our study demonstrates for the first time that these herbs indeed alter the microbiome and produce distinct shifts in microbial populations. This finding is a starting point from which we can begin to decipher how the microbiota may change the gut biochemistry to promote and protect our health.” 

Digestive disorders, including Crohn’s disease, celiac disease and irritable bowel syndrome (IBS), are increasingly prevalent in Western populations. More than 60 million people are affected in the United States alone. Treatments for the disorders are limited.

In the study, the scientists collected stool samples from 12 healthy men and women between the ages of 30 and 60 who ate a vegetarian or vegan diet. The samples were grown in medium (food for bacteria) supplemented with turmeric, ginger, black pepper or long pepper. Genomic sequencing was then used to identify how the abundance of species within the community was altered by the herbal supplement. 

The scientists found that all of the herb-supplemented samples had unique proportions of bacterial families compared to control cultures—indicating the herbs altered the gut microbiome. 

“We are exploring how different herbs produce distinct microbial signatures in the gut,” says Peterson. “It’s clear from this study that each herb works differently. Now the task is to make the connections between the herb profiles and gut health.” 

Next, the researchers plan to test the herbs’ therapeutic potential in a controlled human clinical trial. In parallel, they will work in the lab to dissect the herbs’ molecular components and study how these components influence the gut microbiome and promote digestive health.

“By delving deeper into the beneficial molecules present in these herbs and how microbes may alter those constituents, we may be able to enhance their potential benefit and help people suffering from serious digestive disorders,” explains Peterson.  


The first author of the study is Christine T. Peterson, PhD, of UC San Diego. 

Additional authors include Dmitry A. Rodionov, PhD, of Sanford Burnham Prebys and the Russian Academy of Sciences; Stanislav N. Iablokov of the Russian Academy of Sciences and Yaroslavl State University; Meredith A. Pung, PhD, and Paul J. Mills, PhD, of UC San Diego; Deepak Chopra, MD, of UC San Diego and the Chopra Foundation. Deepak Chopra is the founder of the Chopra Foundation and Chopra Center and a co-owner of the Chopra Center. Mills is the director of research for the Chopra Foundation.

The research was supported by the Samuel Lawrence Foundation, the Chopra Foundation and the Russian Science Foundation (19-14-00305).

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How can prebiotics help your gut health?

AuthorAnjali Gupta
Date

April 16, 2018

Walk down the refrigerated section of any grocery store aisle and you’ll see shelves lined with yogurt containers screaming out the benefits of probiotics—the ‘good bacteria’ that help with digestion. Words like microbriome, gut health, and probiotics are now part of our common vocabulary. But, little has been mentioned about “prebiotics”!

In low concentrations in foods like onions, garlic, chicory root, and bananas—they usually reach the colon undigested. In the colon, prebiotics are broken down into smaller carbohydrates or “carbs” as we usually say. Probiotics eat these ‘carbs’ creating positive health effects—such as improved colon functions, reduced inflammation and protection from infections. In this way, prebiotics and probiotics work together to promote gastrointestinal health.

Scott Peterson PhD, professor at SBP, recently worked with UC San Diego and The Chopra Foundation to assess the prebiotic effects of three herbs (slippery elm, licorice and triphala) that are commonly used in Ayurvedic medicine—a system that has been practiced in India for over 5,000 years.

“Very few scientific and clinical studies have been done to test the effectiveness of these herbal medicines,” says Peterson. “We wanted to see how these herbs affect the growth and population of 300 species of bacteria commonly found in the gut.

Peterson’s team looked at fecal samples collected from 12 healthy middle-aged men and women who ate a vegetarian or vegan diet. The team wanted to know how the bacterial populations in the gut change when exposed to the medicinal herbs.

“We were surprised at the extent and complexity of the changes in the gut microbiota composition,” says Peterson. “And the species most positively impacted by the herbal supplements were predominantly species with documented health-promoting qualities.

“This study, published in the Journal of Alternative and Complementary Medicine, highlights the significant prebiotic potential of herbal medicines and suggests that the health benefits of these herbs are due, at least in part, to their ability to modulate the gut microbiota in manner linked to improved gastrointestinal health,” explains Peterson.

“You can’t patent an herb. But there is an opportunity to combine prebiotics and herbs into potential medicines. If we can use natural therapy to reduce inflammation for example, then it may change the effectiveness of certain drugs used to treat obesity, type 2 diabetes or inflammatory bowel disease (IBD).”

Considering that about 65 million Americans suffer from disorders of the gut, novel evidence-based medicines may offer new options for relief. The researchers are already planning to test these herbs in a controlled human clinical trial.

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Scott Peterson receives grant to discover gut microbiome-targeted therapies

AuthorJessica Moore
Date

January 17, 2017

The gut microbiome—the trillions of bacteria and other microscopic bugs in your intestine—is a hot topic in medical research. The number scientific studies showing that the balance of microbes affects health not just in the GI tract, but throughout the body is growing rapidly. Motivated by these findings, Scott Peterson, PhD, professor at Sanford Burnham Prebys Medical Discovery Institute, is searching for ways to manipulate the microbiome to treat disease.

Because his work is so pioneering, he recently won a grant from the William Randolph Hearst Foundation to support a graduate student, Lisa Elmén, to carry out some very ambitious research. She’s looking for prebiotics—compounds that affect the makeup of the microbiome because they’re metabolized by some bacteria more than others—that can address underlying drivers of inflammatory diseases like obesity, type 2 diabetes, Crohn’s and colitis, autoimmune conditions and food allergies.

Despite their diversity, these diseases all have a connection to the gut—they’re associated with increased inflammation and permeability, or leakiness, of the intestine. That’s bad because it means foreign molecules from food and microbes can get into the bloodstream, which can trigger or worsen inflammation and cause the immune system to go awry. The main question Elmén will address is whether prebiotics effectively improve barrier function and whether this slows or even reverses disease progression.

“We’ve already identified a number of compounds that alter the gut microbiome in a way that we believe correlates with better intestinal integrity,” says Peterson. “This award will let us move on to the next steps, including examining whether these prebiotics alter disease severity.”

“It would have been very challenging to get this work funded through more traditional avenues, so this award is critical to advancing our research,” Peterson adds. “Leaky gut isn’t a widely recognized condition, and few clinicians test for it despite evidence that it contributes to disease. The prebiotics we hope to find could improve the health of millions of Americans.”

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Targeting gut microbes may help malnourished children grow

Authorjmoore
Date

March 7, 2016

Malnutrition in infants and young children can have major life-long impacts—deficiencies in important nutrients stunt growth and impair development. Although aid organizations have developed fortified meals to make up for these deficiencies, they don’t completely compensate for the lack of nutrition. Now scientists know why malnourished children might not benefit as much as they should from added nutrients in their diet. Continue reading “Targeting gut microbes may help malnourished children grow”