AgriLife Research investigates “mechanics”


Media inquiries to Laura Muntean, [email protected], 6012481891

Written by Paul Schattenberg, Cell: 210-859-5752; MSTeams: 210-890-4548, pa [email protected]

Texas A&M AgriLife Research has received a one-year grant of $632,593 from the National Center for Complementary and Integrative Health, NCCIH, for a study of complementary and alternative medicine.

Susanne Talcott, Ph.D., in the Texas A&M Department of Food Science and Technology, will be one of the principal investigators for the new study on botanical compounds and gut inflammation. (Photo by Texas A&M AgriLife)

One of the principal investigators on the study, titled “Anti-inflammatory Microbiome-Substrate-Host Interactions,” will be Susanne Talcott, Ph.D., Associate Professor of AgriLife Research in the Department of Food Science and Technology at Texas A&M College of Agriculture and Life Sciences, Bryan College Station. She will work with Robert Britton, Ph.D., Baylor College of Medicine in Houston, and Stephen Talcott, Ph.D., also in Texas A&M’s Division of Food Science and Technology.

“This is a short-term, high-priority project,” Talcott said. “The National Institutes of Health has invested millions in the clinical study of plant compounds, particularly dietary phenols. However, to date, most human clinical intervention studies with these compounds have not yielded consistent results.”

She said age and obesity are associated with a reduced ability of the gut microbiome to produce absorbable metabolites from polyphenols.

“This means that the very population that needs the anti-inflammatory properties of fruits and vegetables may not benefit optimally,” she said.

The NCCIH is part of the National Institutes of Health, NIH, in the US Department of Health and Human Services. Talcott said the year-long grant is a bridge to a larger pending application for nearly $4 million in funding.

What are polyphenols?

Polyphenols are a number of healthy substances found in fruits, green tea, spices, nuts and other foods. The largest subgroup of polyphenols that humans ingest from food are substances called gallotannins. Human gut microbiomes vary and process polyphenols differently, and emerging evidence suggests this fact has contributed significantly to inconclusive human clinical trials of polyphenols.

“Studies have shown that microbial metabolites have anti-inflammatory effects through cell signaling, but only in individuals who actually have bacteria in their gut microbiome that can break down gallotannins into smaller absorbable anti-inflammatory metabolites,” Talcott explained.

She said a lack of understanding of the causes of the person-to-person variability underlying the effectiveness of natural products weighs on human clinical trials that assess the biological signatures that indicate improved resistance to chronic disease.

“The NCCIH is trying to better understand if and how these plant compounds may be effective in reducing inflammation,” she said.

The purpose of the study

Talcott said the long-term goal of this new project is to help develop novel recommendations for the safe and effective consumption of large molecular weight polyphenols. This includes studying gallotannins and other anti-inflammatory polyphenols as part of a precision nutrition approach to resilience to inflammation.

“Gallotannins themselves are not metabolized directly by humans, but are substrates for selected bacteria in the human gastrointestinal tract,” explained Talcott. “Gallotannin metabolism produces bioavailable anti-inflammatory metabolites, but the levels of these metabolites show large inter-individual variability.”

Proof-of-principle model of polyphenol metabolism and anti-inflammatory response. (Illustration courtesy of Susanne Talcott)

She said polyphenol metabolism may be impaired in individuals with chronic gut inflammation, which could be addressed by supplementation with targeted probiotics.

“Two well-defined enzymatic steps by gut microbes provide the major bioactive metabolites of gallotannins,” she said. “These are tannase and tannin acyl hydrolase GA decarboxylase.”

She said that both enzymes are active in the Lactobacillus plantarum strain and provide a suitable model to study gallotannin metabolism.

“We hope to define the underlying microbial molecular basis for the inter-individual variability in the intestinal anti-inflammatory effects of gallotannins.”

She said the study will develop a proof-of-principle model using knock-out versions of the Lactobacillus plantarum strain, which naturally encodes both enzymes and represents an optimal model for gallotannin metabolism.

“Our central hypothesis is that the interindividual differential microbial metabolism of gallotannins is a significant determinant of their anti-inflammatory activities in relation to intestinal inflammation,” she said.

Talcott said that finding a mechanistic determination of how substrate-microbiome-host interactions affect the anti-inflammatory activities of gallotannins will allow the development of formal science-based intake recommendations, or dosages, for botanical polyphenols.

“Principles from this study can be applied to human clinical trials and advance the scientific basis for dosing recommendations for gallotannins and other polyphenols to increase resistance to chronic inflammatory diseases,” she said.

Growth in the use of botanical supplements

The NIH estimates that the intake of herbal supplements has steadily increased and was a $7 billion industry in 2018, despite the lack of science-based intake recommendations. At the same time, the incidence of inflammatory bowel disease, including Crohn’s disease, and ulcerative colitis affected 1.6 million people in the same year.

The global botanicals market is expected to exceed US$49 billion by 2027, with many of the dietary supplements based on a polyphenolic bioactive, despite the lack of human clinical evidence demonstrating consistent pharmacokinetics and efficacy in the prevention of a wide range of diseases, including inflammatory bowel disease, demonstrate.

“Where standard medications are associated with severe side effects and drug compliance is poor, many patients are looking to alternative herbal remedies, such as prebiotic and probiotic therapies, with the aim of improving resilience to chronic inflammation,” Talcott said. “Hence, despite scarce scientific data to support the effectiveness of these remedies in reducing inflammation, sales of herbal supplements are increasing.”



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