Fiber for Frailty—Strengthening the Microbiome Muscle Axis

There seems to be a microbiome “signature” of frailty. Fecal samples from frail individuals show a striking lack of bacterial diversity, and in particular a deficit of fiber-eating “good bacteria” such as lactobacillus.

But is this a cause or consequence of frailty? For example, those institutionalized in long-term care facilities like nursing homes were found to be fed lower-fiber diets, which alone could help explain the gut findings or contribute to further deterioration. Antibiotic use in older hospitalized patients could also be a confounder or contributor. Exercise alone is associated with a more favorable microbiome profile. However, extraordinary experimental findings do suggest that the impact of gut bacteria on the musculature—for good or ill—can indeed be cause-and-effect.

Our first indication of the importance of the gut-muscle axis came from germ-free mice raised in “bubble boy”-style sterile conditions. With no gut microbiome at all they suffered from shrunken muscles. We know this is cause-and-effect because the muscle impairments can be reversed with a fecal transplant from regular mice, as can a similar induction of muscle atrophy with antibiotics upon reseeding with pre-antibiotic flora.

Fecal transplant studies, in which the guts of individuals are populated with the microbiomes of others, have elevated the field from a conundrum of correlations to concrete causality. This has led to many surprises. For example, the microbiome of malnourished children was assumed to just be a consequence of their severely restricted diets, but mice colonized with their gut bacteria exhibit stunted growth compared to feeding the mice fecal matter from healthy kids. Even weirder, transplanting the gut bugs of pigs into mice changed the distinct muscle fiber characteristics of the mice to become more pig-like. “This raises the possibility,” the researchers speculated, “that faecal microbial transplantation could be used as a means to transmit muscle fibre characteristics between humans, perhaps even from young to old, as a means of improving skeletal muscle function.”

Researchers in Boston compared the strength of mice fed stool from high-functioning men and women in their 70s and 80s to mice fed stool from age-matched low-functioning individuals. And you guessed it, the high-functioning fecal-fed mice were made mightier. This implies that the good gut bugs aren’t just a consequence of healthier elders eating healthier, but they may play an active role in their vitality.

Seed fecal bacteria from marathon runners into mice and it enhances their treadmill running capacity. Before you start nagging Rich Roll for a sample, realize that these performance associated bugs are fiber feeders, and so just eating more fiber-rich foods may do the trick. These good bacteria take fiber and use it to make the anti-inflammatory short chain fatty acid butyrate that is absorbed from your colon into your bloodstream to circulate throughout your body. Just feeding butyrate straight to old mice protects against age-related muscle loss, thus connecting the final dots of the gut-muscle axis.

So, is fiber consumption associated with greater muscle mass maintenance among older adults? Yes, and furthermore, randomizing elderly subjects to eat a diet characterized by higher whole grain and legume consumption—the two foods most concentrated with prebiotics like fiber—modulates their gut bacteria away from the frailty microbiome profile. To prove it, a randomized, double-blind clinical trial of prebiotics for older men and women (average age about 74) significantly improved two frailty criteria—exhaustion and handgrip strength—more than placebo. While frailty index scores worsened in most of the control group, they improved in 89 percent of the prebiotic group, though only 18 percent showed reductions that were considered clinically meaningful after 13 weeks.

What about giving people good bacteria directly? Since those with high frailty scores have 26 times fewer lactobacilli in their gut, why not try giving them some lactobacillus probiotics? After a lactobacillus strain isolated from Taiwanese kimchi (fermented cabbage) was found to increase grip strength in mice, researchers tried giving it to people.

After six weeks of supplementation young men and women gained significantly higher endurance (a remarkable 58 percent increase in time-to-exhaustion on a maximum treadmill running test compared to placebo), in addition to a significant increase in lean mass. But what about in frail older adults? Unfortunately, the probiotics couldn’t significantly beat out placebo for muscle mass or strength, walking speed, or chair stand test timing. But after 18 weeks of supplementation the probiotics were able to improve one measure of performance, the “timed up and go” test. But it’s probably preferable to foster the growth of our own fiber feeders by feeding them fiber, which has the dual benefit of also cutting down on the toxins produced by some of our bad bugs like indoxyl sulfate.

Indoxyl sulfate is a “notorious” pro-inflammatory toxin that results from the putrefaction of protein in the colon. It is thought to play a role in the muscle wasting that accompanies chronic kidney disease. As levels build up it can cause oxidative stress, inflammation and, at least in mice and muscle cells in a petri dish, upregulate genes such as myostatin that are involved in muscle breakdown. Even with healthy kidneys, though, those randomized to just two weeks of a high protein diet (1.9 g/kg of body weight) can suffer a significant rise in blood levels of indoxyl sulfate compared to consuming recommended protein levels.

Fiber can bring it down though. Randomized controlled trials have shown that fiber can significantly lower blood levels of indoxyl sulfate. The thought is that since fiber is such a powerful prebiotic in the colon, protein is diverted from putrefaction into building bacterial mass. Vegetarians only have about half the levels of this toxin in their bloodstream. This can be attributed to their higher fiber/protein intake ratio and the fact that indoxyl sulfate is a breakdown product of the amino acid tryptophan, which tends to be lower among those eating plant protein.

High fat or high protein intake can also reduce the number of good probiotic bacteria like Bifidobacterium. Adding 20 grams of whey and beef protein powder a day for 10 weeks can cause about a fourfold drop in Bifidobacterium abundance, leading to the suggestion that those increasing their protein should consider ramping up fiber-rich foods such as whole grains to compensate.