microbiome Archives - Sanford Burnham Prebys
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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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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”

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New method to identify bacteria in the gut may facilitate development of probiotics

Authorjmoore
Date

January 19, 2016

The gut microbiome, the community of bacteria living in the intestines, has an enormous impact on human health, affecting risk for obesity, inflammatory bowel disease (IBD), neurological disorders, and even cancer. Accordingly, there has been an explosion of research in this area in the past ten years, with the long-term goal of developing ways to manipulate the microbiome to promote the survival of bacteria that promote health and/or eliminate those associated with disease. Continue reading “New method to identify bacteria in the gut may facilitate development of probiotics”

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Sanford-Burnham’s 36th Annual Symposium: The Microbiome and Human Health

Authorsgammon
Date

November 3, 2014

On Thursday, October 30, 2014, Sanford-Burnham hosted more than 250 attendees at its 36th annual symposium to hear opinion-leading scientists discuss their latest findings on the microbiome. The microbiome is a relatively new frontier for research scientists with aims to understand how the trillions of microbes—bacteria, viruses, fungi, and others—that live in our nose, mouth, gut, and skin interact with human cells to influence health and disease. Continue reading “Sanford-Burnham’s 36th Annual Symposium: The Microbiome and Human Health”