In different countries' national dietary guidelines, red meats (beef, pork, and lamb) are often confined to a very small corner. Swedish officials, for example, advise the population to "eat less red and processed meat". Experts in Greece recommend consuming no more than four servings of red meat — not per week, but per month.
"Humans 100% rely on the microbes to digest this food."
Yet somehow, the matter is far from settled. Quibbles over the scientific evidence emerge on a regular basis — as in a recent BMJ article titled, "No need to cut red meat, say new guidelines." News headlines lately have declared that limiting red meat may be "bad advice," while carnivore diet enthusiasts boast about the weight loss and good health they've achieved on an all-meat diet. The wildly successful plant-based burgers? To them, a gimmick. The burger wars are on.
Nutrition science would seem the best place to look for answers on the health effects of specific foods. And on one hand, the science is rather clear: in large populations, people who eat more red meat tend to have more health problems, including cardiovascular disease, colorectal cancer, and other conditions. But this sort of correlational evidence fails to settle the matter once and for all; many who look closely at these studies cite methodological shortcomings and a low certainty of evidence.
Some scientists, meanwhile, are trying to cut through the noise by increasing their focus on the mechanisms: exactly how red meat is digested and the step-by-step of how this affects human health. And curiously, as these lines of evidence emerge, several of them center around gut microbes as active participants in red meat's ultimate effects on human health.
Dr. Stanley Hazen, researcher and medical director of preventive cardiology at Cleveland Clinic, was one of the first to zero in on gut microorganisms as possible contributors to the health effects of red meat. In looking for chemical compounds in the blood that could predict the future development of cardiovascular disease, his lab identified a molecule called trimethylamine-N-oxide (TMAO). Little by little, he and his colleagues began to gather both human and animal evidence that TMAO played a role in causing heart disease.
Naturally, they tried to figure out where the TMAO came from. Hazen says, "We found that animal products, and especially red meat, were a dietary source that, [along with] gut microbes, would generate this product that leads to heart disease development." They observed that the gut microbes were essential for making TMAO out of dietary compounds (like red meat) that contained its precursor, trimethylamine (TMA).
So in linking red meat to cardiovascular disease through TMAO, the surprising conclusion, says Hazen, was that, "Without a doubt, [the microbes] are the most important aspect of the whole pathway."
"I think it's just a matter of time [before] we will have therapeutic interventions that actually target our gut microbes, just like the way we take drugs that lower cholesterol levels."
Other researchers have taken an interest in different red-meat-associated health problems, like colorectal cancer and the inflammation that accompanies it. This was the mechanistic link tackled by the lab of professor Karsten Zengler of the UC San Diego Departments of Pediatrics and Bioengineering—and it also led straight back to the gut microbes.
Zengler and colleagues recently published a paper in Nature Microbiology that focused on the effects of a red meat carbohydrate (or sugar) called Neu5Gc.
He explains, "If you eat animal proteins in your diet… the bound sugars in your diet are cleaved off in your gut and they get recycled. Your own cells will not recognize between the foreign sugars and your own sugars, because they look almost identical." The unsuspecting human cells then take up these foreign sugars — spurring antibody production and creating inflammation.
Zengler showed, however, that gut bacteria use enzymes to cleave off the sugar during digestion, stopping the inflammation and rendering the sugar harmless. "There's no enzyme in the human body that can cleave this [sugar] off. Humans 100% rely on the microbes to digest this food," he says.
Both researchers are quick to caution that the health effects of diet are complex. Other work indicates, for example, that while intake of red meat can affect TMAO levels, so can intake of fish and seafood. But these new lines of evidence could help explain why some people, ironically, seem to be in perfect health despite eating a lot of red meat: their ideal frequency of meat consumption may depend on their existing community of gut microbes.
"It helps explain what accounts for inter-person variability," Hazen says.
These emerging mechanisms reinforce overall why it's prudent to limit red meat, just as the nutritional guidelines advised in the first place. But both Hazen and Zengler predict that interventions to buffer the effects of too many ribeyes may be just around the corner.
Zengler says, "Our idea is that you basically can help your own digestive system detoxify these inflammatory compounds in meat, if you continue eating red meat or you want to eat a high amount of red meat." A possibly strategy, he says, is to use specific pre- or probiotics to cultivate an inflammation-reducing gut microbial community.
Hazen foresees the emergence of drugs that act not on the human, but on the human's gut microorganisms. "I think it's just a matter of time [before] we will have therapeutic interventions that actually target our gut microbes, just like the way we take drugs that lower cholesterol levels."
He adds, "It's a matter of 'stay tuned', I think."