The Top Five Mysteries of the Human Gut Microbiome
A scholar of science, circa 2218, might look back on this era and wonder why, all of a sudden, scientists became so obsessed with human stool. Or more accurately, the microorganisms therein.
Although every human is nearly identical genetically, each person carries around a massively different variety of microbial genes from bacteria, fungi, viruses, and archaea.
This scholar might find, for example, the seven-fold increase in PubMed articles on "gut microbiome" in the half-decade between 2012 and 2017; the plastic detritus of millions of fecal sample collection kits, and evidence that freezers in research labs worldwide had filled up with fecal samples. What's happened?
Human genome science has led to some important medical insights over time. Now it's moving over for the microorganisms. Because, although every human is nearly identical genetically, each person carries around a massively different variety of microbial genes from bacteria, fungi, viruses, and archaea—genes that are collectively called the microbiome.
Thinking that more knowledge about the gut microbiome is going to solve every problem in medicine is pure hubris. And yet these microorganisms seem to be at the nexus of humans and our environment, capable of changing us metabolically and adjusting our immune systems. What might they have the power to do?
Here are five of the most important questions that lie ahead for microbiome science.
1) What makes a gut microbiome 'healthy'?
The words "healthy microbiome" should raise a red flag. Because, currently, if scientists examine the gut microbial community of a single individual they have no way of knowing whether or not it qualifies as healthy—nor even what parameter to look at in order to find out. Is it only the names of the bugs that matter, or is it their diversity? Alternatively, is it function—what they're genetically equipped to do?
The words "healthy microbiome" should raise a red flag.
The focused efforts of the Human Microbiome Project were supposed to accomplish the apparently simple task of defining a healthy microbiome, but no clear answers emerged. If researchers could identify the parameters of a healthy microbiota per se, they might have a way to know whether manipulations—from probiotics to fecal transplant—were making a difference that could lead to a good health outcome.
2) Diet can manipulate gut microbes. How does this affect health?
"Many kinds of bacteria in our gut, they're changeable by changing our diet," says Liping Zhao of Shanghai Jiao Tong University in China, citing two large population studies from 2016. What's murkier is how this effects a change in health status.
Zhao's research focuses on making the three-way link between diet, gut microbiota, and health outcome. Meanwhile, researchers like Genelle Healey at the University of British Columbia (UBC) are working to track how the gut microbiome and health respond to a dietary intervention in a personalized way.
Knowing how the diet-induced changes in gut microbes affected health in the long term would allow every individual to toss out the diet books and figure out a dietary pattern—probably as personal as their gut microbes—that would result in their best health down the line.
If scientists could find how to harness one or more microorganisms to have specific effects on the immune system, they might be able to crack a new class of therapeutics.
3) How can gut microorganisms be used to fine-tune the immune system?
Many chronic diseases—autoimmune conditions but also, according to the latest research, obesity and cardiovascular disease—are immune mediated. Kenya Honda of Keio University School of Medicine in Tokyo, Yasmine Belkaid of the US National Institutes of Health (NIH), June Round at University of Utah, and many other researchers are chasing the ways in which gut microbes 'talk' to the immune system. But it's more than just studying certain bugs.
"It's an incredibly complex situation and we can't just label bugs as pro-inflammatory or anti-inflammatory. It's very context-dependent," says Justin Sonnenburg of Stanford. But if scientists could find how to harness a microorganism or group of them to have specific effects on the immune system, they might be able to crack a new class of therapeutics that could change the course of immune-mediated diseases.
4) How can a person's gut microbiome be reconfigured in a lasting way?
Measures of the adult microbiome over time show it has a high degree of stability—in fact, it can be downright stubborn. But a new, stable gut microbial ecology can be achieved when someone receives a fecal transplant for recurrent C. difficile infection. Work by Eric Alm of Massachusetts Institute of Technology (MIT) and others have shown the recipient's gut microbiota ends up looking more like the donor's, with engraftment of particular strains.
But what are the microorganisms' 'rules of engraftment'? Knowing this, it might be possible to intervene in a number of disease-associated microbiome states, changing them in a way that changed the course of the disease.
Is the infant microbiome, as shaped by birth mode and diet, responsible for health issues later in life?
5) How do early-life shapers of the gut microbiome affect health status later on?
Researchers have found two main factors that appear to shape the gut microbiome in early life, at least temporarily: mode of birth (whether vaginal or Cesarean section), and early life diet (whether formula or breast milk). These same factors are associated with an increased risk of immune and metabolic diseases. So is the infant microbiome, as shaped by birth mode and diet, responsible for health issues later in life?
Brett Finlay of the University of British Columbia has made these 'hygiene hypothesis' compatible links between the absence of certain bacteria in early life and asthma later on. "I think the bugs are shaping and pushing how our immune system develops, and if very early in life you don't have those things, it goes to a more allergic-type immune system. If you do have those bugs it gets pushed towards more normal," he says. The work could lead to targeted manipulation of the microbiome in early life to offset negative health effects.
By the time you reach for that head of lettuce at the grocery store, it's already probably traveled hundreds of miles and spent almost two weeks sitting in a truck.
"Food is no longer grown for human beings, it's grown for a truck to support a supply chain," says the president of Metropolis Farms in Philadelphia.
But everyone likes fresh produce, so the closer your veggies are grown to your favorite supermarket or restaurant, the better. With the recent outbreak of E.coli contaminating romaine lettuce across the United States, it's especially appealing to know that your produce has been grown nearby in a safe environment. How about a farm right on top of a grocery store in Philadelphia? Or one underground in the heart of Manhattan? Or one inside an iconic restaurant in Australia?
Hyper-local urban farming is providing some consumers with instant access to seriously fresh produce. It's also a way for restaurants and food suppliers to save on costs, eliminating the need for expensive packaging and shipping, experts say. Tour five of the world's coolest vertical farms in pictures below.
NEW YORK
Farm.One's vision is to build small indoor farms in cities around the country that provide rare herbs and produce to high-end restaurants. Their farm in the heart of Manhattan occupies 1200 square feet in a basement beneath the two-Michelin-starred restaurant Atera, which is conveniently one of their customers. All of the 20 to 25 restaurants they supply to are within a three-mile radius, making delivery possible by subway or bike.
"We have a direct connection with the chefs," says the CEO and founder Robert Laing. "For very perishable produce like herbs and leafy greens, hyper-local vertical farming works really well. It's literally dying the moment you cut it, and this is designed to be fresh."
PHILADELPHIA
"Restaurants are important," says Jack Griffin, the president of the indoor vertical Metropolis Farms in Philadelphia. "But not the most important, because they don't feed the majority of people."
Griffin is on a mission to standardize the indoor farming industry so supermarkets and communities around the world can benefit from the technology in a cost-effective and accessible way. Right now, Metropolis Farms supplies to a local grocer, Di Brunos Bros, that is less than two miles from their facility. In the future, they have plans to build a rooftop greenhouse atop a new supermarket in Philadelphia, plus indoor farms in Baltimore, Oklahoma, and as far away as India.
One advantage of their farms, says Griffin, is their proprietary technology. An adaptive lighting system allows them to grow almost any size crop, including tomatoes, cucumbers, peppers, strawberries, and even giant sunflowers.
"It's bigger than just food," he explains. "We are working on growing specialty crops like wine, chocolate, and coffee. All these plants are within reach, and we can cut the cord between supply chains that are difficult to deal with. Can you imagine if you grew Napa wines in Camden, New Jersey?"
BERLIN
GOOD BANK, in Berlin, bills itself as the world's first farm-to-table vertical restaurant. They grow their many of their own vegetables and salads onsite using farming system technology from another German company called INFARM. The latter's co-founder and CEO, Erez Galonska, cites a decline in traditional farming, an increase in urban populations, and the inefficiency of the current food system as motivation for turning to vertical farming to produce food where people actually eat and live.
"INFARM is pioneering on-demand farming services to help cities become self-sufficient in their food production, while eliminating waste and reducing their environmental impact," Galonska says.
MELBOURNE
Melbourne-based Farmwall leases indoor vertical farms the size of small bookshelves to restaurants and cafes. The farms are designed to be visually appealing, with fish tanks at the bottom supplying nutrient-rich water to the hemp media in which herbs and microgreens grow under LED lights. As part of the subscription model, urban farmers come once a week to check water levels, bring new trays of greens, and maintain the system. So far, two restaurants have signed up -- Top Paddock, in the suburb of Richmond, and Higher Ground, an internationally recognized restaurant in Melbourne.
"It's worth it to the restaurants because they get fresh produce at their fingertips and it has all the benefits of having a garden out back without any of the work," says Serena Lee, Farmwall's co-founder and chief communications officer.
The sky's the limit for future venue possibilities: nursing homes, schools, hotel lobbies, businesses, homes.
"Urban farming is never going to feed the world," Lee acknowledges. "We understand that and we're not saying it will, but when people are able to watch their food grow onsite, it triggers an awareness of local food production. It teaches people about how technology and science can work in coherence with nature to create something super-efficient, sustainable, and beautiful."
LOS ANGELES
At the restaurant Otium in Los Angeles, a peaceful rooftop garden sits atop a structure of concrete and steel that overlooks the hustle and bustle of downtown LA. Vegetables and herbs grown on the roof include Red Ribbon Sorrel, fennel fronds, borage blossoms, nasturtium, bush basil, mustard frills, mustard greens, kale, arugula, petit leaf lettuce, and mizuna. Chef Timothy Hollingsworth delights in Otium's ability to grow herbs that local purveyors don't offer, like the wild Middle Eastern Za'atar he uses on grilled steak with onions and sumac.
"I don't think this growing trend [of urban farming] is something that will be limited to a handful of restaurants," says Hollingsworth. "Every business should be concerned with sustainability and strive to protect the environment, so I think we will be seeing more and more gardening efforts throughout the country."
Whether a garden is vertical or horizontal, indoors or outdoors, on a roof or in a basement, tending to one provides not only fresh food, but intangible benefits as well.
"When you put your time and love into something," says Hollingsworth, "it really makes you respect and appreciate the produce from every stage of its life."
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
The rise of remote work is a win-win for people with disabilities and employers
Disability advocates see remote work as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike.
Any corporate leader would jump at the opportunity to increase their talent pool of potential employees by 15 percent, with all these new hires belonging to an underrepresented minority. That’s especially true given tight labor markets and CEO desires to increase headcount. Yet, too few leaders realize that people with disabilities are the largest minority group in this country, numbering 50 million.
Some executives may dread the extra investments in accommodating people’s disabilities. Yet, providing full-time remote work could suffice, according to a new study by the Economic Innovation Group think tank. The authors found that the employment rate for people with disabilities did not simply reach the pre-pandemic level by mid-2022, but far surpassed it, to the highest rate in over a decade. “Remote work and a strong labor market are helping [individuals with disabilities] find work,” said Adam Ozimek, who led the research and is chief economist at the Economic Innovation Group.
Disability advocates see this development as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike. For decades before the pandemic, employers had refused requests from workers with disabilities to work remotely, according to Thomas Foley, executive director of the National Disability Institute. During the pandemic, "we all realized that...many of us could work remotely,” Foley says. “[T]hat was disproportionately positive for people with disabilities."
Charles-Edouard Catherine, director of corporate and government relations for the National Organization on Disability, said that remote-work options had been advocated for many years to accommodate disabilities. “It’s a little frustrating that for decades corporate America was saying it’s too complicated, we’ll lose productivity, and now suddenly it’s like, sure, let’s do it.”
The pandemic opened doors for people with disabilities
Early in the pandemic, employment rates dropped for everyone, including people with disabilities, according to Ozimek’s research. However, these rates recovered quickly. In the second quarter of 2022, people with disabilities aged 25 to 54, the prime working age, are 3.5 percent more likely to be employed, compared to before the pandemic.
What about people without disabilites? They are still 1.1 percent less likely to be employed.
These numbers suggest that remote work has enabled a substantial number of people with disabilities to find and retain employment.
“We have a last-in, first-out labor market, and [people with disabilities] are often among the last in and the first out,” Ozimek says. However, this dynamic has changed, with adults with disabilities seeing employment rates recover much faster. Now, the question is whether the new trend will endure, Ozimek adds. “And my conclusion is that not only is it a permanent thing, but it’s going to improve.”
Gene Boes, president and chief executive of the Northwest Center, a Seattle organization that helps people with disabilities become more independent, confirms this finding. “The new world we live in has opened the door a little bit more…because there’s just more demand for labor.”
Long COVID disabilities put a premium on remote work
Remote work can help mitigate the impact of long COVID. The U.S. Centers for Disease Control and Prevention reports that about 19 percent of those who had COVID developed long COVID. Recent Census Bureau data indicates that 16 million working age Americans suffer from it, with economic costs estimated at $3.7 trillion.
Certainly, many of these so-called long-haulers experience relatively mild symptoms - such as loss of smell - which, while troublesome, are not disabling. But other symptoms are serious enough to be disabilities.
According to a recent study from the Federal Reserve Bank of Minneapolis, about a quarter of those with long COVID changed their employment status or working hours. That means long COVID was serious enough to interfere with work for 4 million people. For many, the issue was serious enough to qualify them as disabled.
Indeed, the Federal Reserve Bank of New York found in a just-released study that the number of individuals with disabilities in the U.S. grew by 1.7 million. That growth stemmed mainly from long COVID conditions such as fatigue and brain fog, meaning difficulties with concentration or memory, with 1.3 million people reporting an increase in brain fog since mid-2020.
Many had to drop out of the labor force due to long COVID. Yet, about 900,000 people who are newly disabled have managed to continue working. Without remote work, they might have lost these jobs.
For example, a software engineer at one of my client companies has struggled with brain fog related to long COVID. With remote work, this employee can work during the hours when she feels most mentally alert and focused, even if that means short bursts of productivity throughout the day. With flexible scheduling, she can take rests, meditate, or engage in activities that help her regain focus and energy. Without the need to commute to the office, she can save energy and time and reduce stress, which is crucial when dealing with brain fog.
In fact, the author of the Federal Reserve Bank of New York study notes that long COVID can be considered a disability under the Americans with Disability Act, depending on the specifics of the condition. That means the law can require private employers with fifteen or more staff, as well as government agencies, to make reasonable accommodations for those with long COVID. Richard Deitz, the author of this study, writes in the paper that “telework and flexible scheduling are two accommodations that can be particularly beneficial for workers dealing with fatigue and brain fog.”
The current drive to return to the office, led by many C-suite executives, may need to be reconsidered in light of legal and HR considerations. Arlene S. Kanter, director of the disability law and policy program at the Syracuse University College of Law, said that the question should depend on whether people with disabilities can perform their work well at home, as they did during Covid outbreaks. “[T]hen people with disabilities, as a matter of accommodation, shouldn’t be denied that right,” Kanter said.
Diversity benefits
But companies shouldn’t need to worry about legal regulations. It simply makes dollars and sense to expand their talent pool by 15% of an underrepresented minority. After all, extensive research shows that improving diversity boosts both decision-making and financial performance.
Companies that are offering more flexible work options have already gained significant benefits in terms of diverse hires. In its efforts to adapt to the post-pandemic environment, Meta, the owner of Facebook and Instagram, decided to offer permanent fully remote work options to its entire workforce. And according to Meta chief diversity officer Maxine Williams, the candidates who accepted job offers for remote positions were “substantially more likely” to come from diverse communities: people with disabilities, Black, Hispanic, Alaskan Native, Native American, veterans, and women. The numbers bear out these claims: people with disabilities increased from 4.7 to 6.2 percent of Meta’s employees.
Having consulted for 21 companies to help them transition to hybrid work arrangements, I can confirm that Meta’s numbers aren’t a fluke. The more my clients proved willing to offer remote work, the more staff with disabilities they recruited - and retained. That includes employees with mobility challenges. But it also includes employees with less visible disabilities, such as people with long COVID and immunocompromised people who feel reluctant to put themselves at risk of getting COVID by coming into the office.
Unfortunately, many leaders fail to see the benefits of remote work for underrepresented groups, such as those with disabilities. Some even say the opposite is true, with JP Morgan CEO Jamie Dimon claiming that returning to the office will aid diversity.
What explains this poor executive decision making? Part of the answer comes from a mental blindspot called the in-group bias. Our minds tend to favor and pay attention to the concerns of those in the group of people who seem to look and think like us. Dimon and other executives without disabilities don’t perceive people with disabilities to be part of their in-group. They thus are blind to the concerns of those with disabilities, which leads to misperceptions such as Dimon’s that returning to the office will aid diversity.
In-group bias is one of many dangerous judgment errors known as cognitive biases. They impact decision making in all life areas, ranging from the future of work to relationships.
Another relevant cognitive bias is the empathy gap. This term refers to our difficulty empathizing with those outside of our in-group. The lack of empathy combines with the blindness from the in-group bias, causing executives to ignore the feelings of employees with disabilities and prospective hires.
Omission bias also plays a role. This dangerous judgment error causes us to perceive failure to act as less problematic than acting. Consequently, executives perceive a failure to support the needs of those with disabilities as a minor matter.
Conclusion
The failure to empower people with disabilities through remote work options will prove costly to the bottom lines of companies. Not only are limiting their talent pool by 15 percent, they’re harming their ability to recruit and retain diverse candidates. And as their lawyers and HR departments will tell them, by violating the ADA, they are putting themselves in legal jeopardy.
By contrast, companies like Meta - and my clients - that offer remote work opportunities are seizing a competitive advantage by recruiting these underrepresented candidates. They’re lowering costs of labor while increasing diversity. The future belongs to the savvy companies that offer the flexibility that people with disabilities need.