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Of Mice and Men

Study with Mice Reveals Potential Human Health Benefits

As they age, people tend to lose strength and muscle mass. It now seems that some of that loss may be related to guts – not fortitude, but the microbes within the gastro-intestinal tract.

Several studies have examined the impact of the gut microbiata (the collection of all microbes found in the stomach and intestines, including bacteria, fungi, viruses, etc.) on muscle in mice, but few studies have followed up with humans. Now, Agricultural Research Service (ARS)-funded research at Tufts University is examining that relationship.

“Gut bacterial composition changes during aging,” said Michael Lustgarten, an ARS-funded scientist on the Nutrition, Exercise Physiology, and Sarcopenia (age-related involuntary loss of skeletal muscle mass and strength) Team at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. Lustgarten is the author and co-author of papers that examined the role of the gut microbiome on skeletal muscle mass and muscle strength in both mice and older adult humans.

In an earlier study, Lustgarten’s group identified a role for the gut microbiome in muscle strength. First, they compared gut bacterial composition among older adult humans who differed in muscle strength. Then, they transplanted fecal samples from these study participants into mice; microbes from the samples “colonized” the mice. The group found that muscle strength was lower in colonized mice with samples that came from people with relatively lower muscle strength, evidence that suggests a role for gut bacteria on muscle strength.

To find out how gut bacteria impact muscle, Lustgarten is examining the metabolites that they produce. Bacteria that produce metabolites that positively impact muscle (in animal models) decrease with age, whereas bacterial metabolites that negatively impact muscle increase with age. With this fact in mind, Lustgarten’s goal is to improve muscle health and function by improving gut bacterial composition, by increasing levels of “good” bacteria and their related metabolites, while simultaneously decreasing levels of bacteria that produce metabolites that negatively impact muscle.

His most recent project aims to improve the gut-muscle axis (the relationship between gut microbiota and muscle) in people in the 70-85 age range. To do so, he evaluated levels of gut bacteria-derived metabolites and muscle-related measures, including whole-body lean mass, thigh muscle composition (the amount of fat contained within and between muscle cells), and physical function (handgrip strength, the time needed to rise and return to a chair five times, and treadmill endurance).

The next project will enroll 24 human subjects, with half consuming an intervention diet of high soluble fiber-containing foods for 12 weeks, with most of the fiber coming from vegetables. The other subjects will consume a control diet, which is based on USDA’s Dietary Guidelines and contains about four times less soluble fiber than the intervention diet. Lustgarten expects that the relatively higher soluble fiber intake in the intervention group will lead to more bacteria with muscle-boosting metabolites, while simultaneously limiting growth of bacteria (and their metabolites) that negatively impact muscle.

Participants will receive baseline evaluations at the beginning of the project, and then will be tested again after 12 weeks on the study diets.

This isn’t the first time that the influence of gut bacteria has been explored; other investigators have identified a role for gut bacteria on the health and/or function of several organ systems in the human body, including the kidney, liver, brain, and immune system.

Lustgarten said that the future looks bright for additional research on gut microbiome influence, and related projects that might help human health. “I believe that we will have targeted bacterial therapeutics that can improve muscle or other organs in the aged, as well as targeted therapeutics that inhibit ‘bad’ bacteria from producing metabolites that can negatively impact human health.” – By Scott Elliott, ARS Office of Communications


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