Gut Microbes Could Finally Settle the Debate Over Whether Red Meat Is Unhealthy

Some people can eat red meat without negative health consequences, which may be due to variability between people's gut microbes.
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."
How to Live With and Love Bugs with Jessica Ware
Entomologist Jessica Ware is using new technologies to identify insect species in a changing climate. She shares her suggestions for how we can live harmoniously with creeper crawlers everywhere.
Jessica Ware is obsessed with bugs.
My guest today is a leading researcher on insects, the president of the Entomological Society of America and a curator at the American Museum of Natural History. Learn more about her here.
You may not think that insects and human health go hand-in-hand, but as Jessica makes clear, they’re closely related. A lot of people care about their health, and the health of other creatures on the planet, and the health of the planet itself, but researchers like Jessica are studying another thing we should be focusing on even more: how these seemingly separate areas are deeply entwined. (This is the theme of an upcoming event hosted by Leaps.org and the Aspen Institute.)
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Entomologist Jessica Ware
D. Finnin / AMNH
Maybe it feels like a core human instinct to demonize bugs as gross. We seem to try to eradicate them in every way possible, whether that’s with poison, or getting out our blood thirst by stomping them whenever they creep and crawl into sight.
But where did our fear of bugs really come from? Jessica makes a compelling case that a lot of it is cultural, rather than in-born, and we should be following the lead of other cultures that have learned to live with and appreciate bugs.
The truth is that a healthy planet depends on insects. You may feel stung by that news if you hate bugs. Reality bites.
Jessica and I talk about whether learning to live with insects should include eating them and gene editing them so they don’t transmit viruses. She also tells me about her important research into using genomic tools to track bugs in the wild to figure out why and how we’ve lost 50 percent of the insect population since 1970 according to some estimates – bad news because the ecosystems that make up the planet heavily depend on insects. Jessica is leading the way to better understand what’s causing these declines in order to start reversing these trends to save the insects and to save ourselves.
Matt Fuchs is the editor-in-chief of Leaps.org. He is also a contributing reporter to the Washington Post and has written for the New York Times, Time Magazine, WIRED and the Washington Post Magazine, among other outlets. Follow him on Twitter @fuchswriter.
They received retinal implants to restore their vision. Then the company turned its back on them.
A company called Second Sight made an implant that partially restored vision to people who'd been blind for decades. But when Second Sight pivoted, it stopped servicing its product, leaving many in the dark.
The first thing Jeroen Perk saw after he partially regained his sight nearly a decade ago was the outline of his guide dog Pedro.
“There was a white floor, and the dog was black,” recalls Perk, a 43-year-old investigator for the Dutch customs service. “I was crying. It was a very nice moment.”
Perk was diagnosed with retinitis pigmentosa as a child and had been blind since early adulthood. He has been able to use the implant placed into his retina in 2013 to help identify street crossings, and even ski and pursue archery. A video posted by the company that designed and manufactured the device indicates he’s a good shot.
Less black-and-white has been the journey Perk and others have been on after they were implanted with the Argus II, a second-generation device created by a Los Angeles-based company called Second Sight Medical Devices.
The Argus II uses the implant and a video camera embedded in a special pair of glasses to provide limited vision to those with retinitis pigmentosa, a genetic disease that causes cells in the retina to deteriorate. The camera feeds information to the implant, which sends electrical impulses into the retina to recapitulate what the camera sees. The impulses appear in the Argus II as a 60-pixel grid of blacks, grays and whites in the user’s eye that can render rough outlines of objects and their motion.
Smartphone and computer manufacturers typically stop issuing software upgrades to their devices after two or three years, eventually rendering them bricks. But is the smartphone approach acceptable for a device that helps restore the most crucial sense a human being possesses?
Ross Doerr, a retired disability rights attorney in Maine who received an Argus II in 2019, describes the field of vision as the equivalent of an index card held at arm’s length. Perk often brings objects close to his face to decipher them. Moreover, users must swivel their heads to take in visual data; moving their eyeballs does not work.
Despite its limitations, the Argus II beats the alternative. Perk no longer relies on his guide dog. Doerr was uplifted when he was able to see the outlines of Christmas trees at a holiday show.
“The fairy godmother department sort of reaches out and taps you on the shoulder once in a while,” Doerr says of his implant, which came about purely by chance. A surgeon treating his cataracts was partnered with the son of another surgeon who was implanting the devices, and he was referred.
Doerr had no reason to believe the shower of fairy dust wouldn’t continue. Second Sight held out promises that the Argus II recipients’ vision would gradually improve through upgrades to much higher pixel densities. The ability to recognize individual faces was even touted as a possibility. In the winter of 2020, Doerr was preparing to travel across the U.S. to Second Sight’s headquarters to receive an upgrade. But then COVID-19 descended, and the trip was canceled.
The pandemic also hit Second Sight’s bottom line. Doerr found out about its tribulations only from one of the company’s vision therapists, who told him the entire department was being laid off. Second Sight cut nearly 80% of its workforce in March 2020 and announced it would wind down operations.
Ross Doerr has mostly stopped using his Argus II, the result of combination of fear of losing its assistance from wear and tear and disdain for the company that brought it to market.
Jan Doerr
Second Sight’s implosion left some 350 Argus recipients in the metaphorical dark about what to do if their implants failed. Skeleton staff seem to have rarely responded to queries from their customers, at least based on the experiences of Perk and Doerr. And some recipients have unfortunately returned to the actual dark as well, as reports have surfaced of Argus II failures due to aging or worn-down parts.
Product support for complex products is remarkably uneven. Although the iconic Ford Mustang ceased production in the late 1960s, its parts market is so robust that it’s theoretically possible to assemble a new vehicle from recently crafted components. Conversely, smartphone and computer manufacturers typically stop issuing software upgrades to their devices after two or three years, eventually rendering them bricks. Consumers have accepted both extremes.
But is the smartphone approach acceptable for a device that helps restore the most crucial sense a human being possesses?
Margaret McLean, a senior fellow at the Markkula Center for Applied Ethics at Santa Clara University in California, notes companies like Second Sight have a greater obligation for product support than other consumer product ventures.
“In this particular case, you have a great deal of risk that is involved in using this device, the implant, and the after care of this device,” she says. “You cannot, like with your car, decide that ‘I don’t like my Mustang anymore,’ and go out and buy a Corvette.”
And, whether the Argus II implant works or not, its physical presence can impact critical medical decisions. Doerr’s doctor wanted him to undergo an MRI to assist in diagnosing attacks of vertigo. But the physician was concerned his implant might interfere. With the latest available manufacturer advisories on his implant nearly a decade old, the procedure was held up. Doerr spent months importuning Second Sight through phone calls, emails and Facebook postings to learn if his implant was contraindicated with MRIs, which he never received. Although the cause of his vertigo was found without an MRI, Doerr was hardly assured.
“Put that into context for a minute. I get into a serious car accident. I end up in the emergency room, and I have a tag saying I have an implanted medical device,” he says. “You can’t do an MRI until you get the proper information from the company. Who’s going to answer the phone?”
Second Sight’s management did answer the call to revamp its business. It netted nearly $78 million through a private stock placement and an initial public offering last year. At the end of 2021, Second Sight had nearly $70 million in cash on hand, according to a recent filing with the Securities and Exchange Commission.
And while the Argus II is still touted at length on Second Sight’s home page, it appears little of its corporate coffers are earmarked toward its support. These days, the company is focused on obtaining federal approvals for Orion, a new implant that would go directly into the recipient’s brain and could be used to remedy blindness from a variety of causes. It obtained a $6.4 million grant from the National Institutes of Health in May 2021 to help develop Orion.
Presented with a list of written questions by email, Second Sight’s spokesperson, Dave Gentry of the investor relations firm Red Chip Companies, copied a subordinate with an abrupt message to “please handle.” That was the only response from a company representative. A call to Second Sight acting chief executive officer Scott Dunbar went unreturned.
Whether or not the Orion succeeds remains to be seen. The company’s SEC filings suggest a viable and FDA-approved device is years away, and that operational losses are expected for the “foreseeable future.” Second Sight reported zero revenue in 2020 or 2021.
Moreover, the experiences of the Argus II recipients could color the reception of future Second Sight products. Doerr notes that his insurer paid nearly $500,000 to implant his device and for training on how to use it.
“What’s the insurance industry going to say the next time this crops up?” Doerr asks, noting that the company’s reputation is “completely shot” with the recipients of its implants.
Perk, who made speeches to praise the Argus II and is still featured in a video on the Second Sight website, says he also no longer supports the company.
Jeroen Perk, an investigator for the Dutch customs service, cried for joy after partially regaining his sight, but he no longer trusts Second Sight, the company that provided his implant.
Nanda Perk
Nevertheless, Perk remains highly reliant on the technology. When he dropped an external component of his device in late 2020 and it broke, Perk briefly debated whether to remain blind or find a way to get his Argus II working again. Three months later, he was able to revive it by crowdsourcing parts, primarily from surgeons with spare components or other Argus II recipients who no longer use their devices. Perk now has several spare parts in reserve in case of future breakdowns.
Despite the frantic efforts to retain what little sight he has, Perk has no regrets about having the device implanted. And while he no longer trusts Second Sight, he is looking forward to possibly obtaining more advanced implants from companies in the Netherlands and Australia working on their own products.
Doerr suggests that biotech firms whose implants are distributed globally be bound to some sort of international treaty requiring them to service their products in perpetuity. Such treaties are still applied to the salvage rights for ships that sunk centuries ago, he notes.
“I think that in a global tech economy, that would be a good thing,” says McLean, the fellow at Santa Clara, “but I am not optimistic about it in the near term. Business incentives push toward return on share to stockholders, not to patients and other stakeholders. We likely need to rely on some combination of corporately responsibility…and [international] government regulation. It’s tough—the Paris Climate Accord implementation at a slow walk comes to mind.”
Unlike Perk, Doerr has mostly stopped using his Argus II, the result of combination of fear of losing its assistance from wear and tear and disdain for the company that brought it to market. At 70, Doerr says he does not have the time or energy to hold the company more accountable. And with Second Sight having gone through a considerable corporate reorganization, Doerr believes a lawsuit to compel it to better serve its Argus recipients would be nothing but an extremely costly longshot.
“It’s corporate America at its best,” he observes.