Gut Instincts

Right before their colonoscopies, with the stress of a bowel prep still rumbling in their bellies and a mental image of the procedure beginning to sharpen, some patients will ask me why I chose a career in gastroenterology: “What made you interested in this?” The reason I usually give is that you could go all your life without a heart problem, or a lung problem, or a kidney problem, but not without a bit of nausea, constipation, or abdominal pain. The work of digestion is part of the rhythm of our daily lives, I tell them, which helps my work feel similarly immediate.

A second reason, one that I usually keep to myself, is that endoscopies are fun. As medical procedures go, they are short and reasonably safe, hygienic but without the fuss of formal sterile technique. They rely on familiarity with a finite stretch of the anatomy, a narrow pink tube roughly thirty feet long, which becomes effortless to navigate after years of practice. Granted, this surface-level inspection works better for certain problems than others. Colonoscopy can diagnose a predisposition to rectal bleeding, for example, far more reliably than issues like diarrhea before public speeches or after heavy meals.

Many patients don’t need me to convince them of the gut’s importance. Years of severe symptoms leave them desperate for answers, especially after routine diagnostic tests come back normal. The primary complaint need not even be located in the abdomen—it could be swollen joints, irritated skin, chronic fatigue—for a patient’s suspicion to settle on the gastrointestinal tract.

Recent popular books and articles have brought attention to the physiological complexity of the gut, and particularly to the gut microbiome, an increasingly familiar term that refers to the trillions of bacteria residing within an individual’s digestive system. Research has shown that these microbes help digest food, reinforce the gut’s protective lining, and regulate the immune system, among other functions. Microbial metabolites—the by-products of bacteria’s metabolic processes—include vitamins essential to synthesizing our blood cells and neurochemical signals that can affect our mood and behavior.

Bacteria coexist in the gut alongside other microorganisms like viruses and fungi, whose numbers are likewise dizzying. Reading about the importance of these varied gastrointestinal contents has driven many patients to fixate on the idea of “gut health,” scrutinizing their bowels well past the limits of an endoscopic examination.

Are they right to do so? As rapidly as gastrointestinal research is advancing, there remains a wide gap between findings that spark scientific interest and those that might change clinical practice.^* Several studies have reported unique microbiome profiles among patients with conditions as diverse as diabetes, anxiety, and osteoarthritis. Other experiments have demonstrated that a narrower range of conditions, like obesity and ulcerative colitis, can be caused in animals by a stool transfer from affected humans.

Various dietary components and patterns—from gluten and artificial sweeteners to intermittent fasting and the Mediterranean diet—have been tied to microbial changes, which in turn have been associated with measurable shifts in molecular markers of inflammation and, in some cases, reduced severity of autoimmune conditions like Crohn’s disease and multiple sclerosis. When we marvel at these observed effects, though, we don’t always consider their size. How does gluten avoidance’s effect on inflammation compare with that of immunosuppressing medications? In a story of complicated illness, it can be easy to confuse footnotes for headlines.

Laboratory measures of intestinal bacteria serve as the foundation of most microbial research, but the state of the microbiome can be reported in several ways: by the density of isolated species and by statistical appraisals of overall diversity; from saliva or stool samples; at a single moment or before and after experimental manipulation. Patterns emerge readily among so many possible variables, which introduces the separate challenge of deciding which of those patterns are meaningful.

Correlations don’t imply causation, as the old epidemiological chestnut goes, nor does statistical significance imply clinical significance. (By some calculations, winning the lottery is significantly associated with the act of buying a ticket.) But the idea that reengineering our gut bacteria could provide a direct route to mitigating disease has captivated clinicians, patients, and entrepreneurs. The global probiotic market is currently valued at over $58 billion, even though evidence-based recommendations on probiotic usage remain equivocal at best.

In the busy field of research into gastrointestinal function, we don’t yet know what clinically valuable signal—if any—will emerge from the noise. Spend enough time on these new medical narratives, though, and the noise itself can become an object of fascination, a kind of Rorschach test for our collective imagination that reveals our fears about the health threats of modern life.

Three recent books are among the latest efforts to illustrate how the gastrointestinal tract presides over the health of the entire body. The gastroenterologist and Columbia University professor Shilpa Ravella’s A Silent Fire argues that “hidden inflammation,” mediated by diet and the microbiome, is a root cause of many contemporary illnesses. These include not only chronic scourges of old age like heart disease, diabetes, and dementia, but also more mysterious illnesses that seem to crop up out of nowhere. Ravella’s opening anecdote centers on a medical school classmate, Jay, who is jolted from seemingly perfect health by a syndrome of progressive neuromuscular weakness that his doctors ultimately deem to be inflammatory in nature. The vignette serves as a warning to others who might be similarly unaware of the dark forces billowing around their insides.

The first half of A Silent Fire serves as a dense primer on inflammation as a biomedical concept. Ravella profiles Nobel laureates alongside a wide cast of inflammatory signals like TNF-α and IL-1β. Her history is meticulous, despite a somewhat narrow vision of the forces that shape it. (“Unlike classical history,” she writes, the history of medicine is “bereft of the narrative framework provided by wars or shifts in political power.”) She discusses famous nineteenth-century figures such as Rudolf Virchow, the German physician widely credited as the founder of modern pathology, and Elie Metchnikoff, the Russian zoologist who discovered how white blood cells neutralize invading bacteria, as well as less familiar researchers like Ruslan Medzhitov, Gökhan Hotamışlıgil, and Luigi Ferrucci. Their studies of cancer, obesity, and aging, respectively, have shed light on what Ravella describes as a “new type of inflammation,” far subtler than what we associate with swollen joints or infected wounds. It’s more like a state of being, “low-level, chronic, and smoldering,” from which several ailments are thought to arise.

For all this careful plotting, though, the book’s rendering of the immune system feels shadowy and unpredictable. Ravella favors anthropomorphic language that subverts the precision of the scientific work she summarizes. Inflammation is “silent and sinister,” “an amorphous foe” with a penchant for “brooding quietly before exploding in a sudden rage.” The second half of the book maps connections among immune function, nutrition, and intestinal microbiota, but with the stage already set for thinking about inflammation as a hazy predisposition, the benefits of plant-based and fermented foods come across as similarly imprecise.

Findings from the scientific literature get disconnected from their methodology, as when “eating a small handful of nuts each day” is said to “lengthen life.” (The studies supporting that claim cross-reference dietary questionnaires with mortality databases, leaving ample room for confounding variables like socioeconomic factors.) Ravella conjures a vast system of pro- and anti-inflammatory influences, from individual proteins to whole foods, that must be kept in equilibrium. For lack of a reliable sense of scale, one begins to wonder whether Jay might have been cured by a few thoughtfully constructed salads. The reader is left with an impression of immune function that is, like the microbiome, malleable enough for us to feel responsible and volatile enough for us to feel constantly at risk.

Contemporary discussions of the gastrointestinal tract often return to an ideal of balance. Concerns about dysbiosis—the putative misalignment between so-called good and bad bacteria—echo the perennial seductions of “humoralism,” a theory of health derived from the ancient concept of harmony among a few core elements like blood and phlegm, versions of which appear in both Eastern and Western medical traditions. Nuanced research suggests that balance is not an especially useful way of thinking about the human microbiome, since certain species are far more important than others and individual health can coexist with a wide range of microbial variation. But even in the scientific literature, a charmingly uncomplicated rhetoric persists. In a 2017 analysis of peer-reviewed publications, the scientist Katarzyna B. Hooks and the philosopher Maureen A. O’Malley found that about half the time, definitions of dysbiosis don’t get much further than vaguely negative ideas of microbial imbalance, which is itself poorly defined.

The term “microbiome” was borrowed from the field of ecology, as were the early analytic methods of microbial research, and an environmental ethos persists in discussions of gut health. Metaphorical resonances—in the idea of a balanced internal ecosystem, for example—can give way to stark conclusions. Ravella proposes that the plant-based diet most beneficial for our gut microbes also happens to be the most environmentally sustainable one. It’s true that industrial livestock production contributes substantially to worldwide greenhouse gas emissions and that global warming poses obvious consequences for our collective health. But routing this argument through the microbiome feels like a needless detour, diminishing the complexity of microbial dynamics by implying that they might benefit from policy reform just as robustly as rising sea levels.

Ravella sees the relationship between climate change and our epidemic of inflammation as compelling enough to write them both a single prescription: “The best weapon against not only most death and disability in the world but also the ongoing destruction of the planet is food.” It’s a model of health that sidelines genetics, stress, violence, infection, addiction, education, and income, among other factors. Would that it were so easy.

Ecological themes run more diffusely through other contemporary accounts of the gut. Flush, by the former microbiologist Bryn Nelson, draws wide-ranging object lessons from human feces, with chapters detailing the utility of stool in fields like epidemiology, anthropology, and civil engineering. Nelson’s style is digressive, which sometimes costs him coherence; I learned more than I needed to about the utility of maggots in forensic investigations and the behavioral economics of composting toilets in shared office spaces. But his primary conclusions return to parallels between the health of our inner and outer landscapes: “There’s no duality between us and nature, our bodies and the natural resources we exploit.” Ecosystems possess common methods for self-correction, he proposes, “whether in a lake or a gut.”

The book equates balance with both sustainability and health, even as contemporary ecology has largely moved beyond such pastoral ideas and toward an understanding of ecosystems as extremely dynamic. For Nelson, the benefits of gastrointestinal harmony extend beyond an individual colon to a collective way of living.

In comparison to Ravella’s somber tone, Nelson’s is often wonderstruck. He extols excrement’s overlooked merits and has a fondness for scatological wordplay (“feces, in short, is the shit”). But there is still an elegiac strain to his discussion of gut bacteria and their constant risk of depletion. Nelson approvingly cites the work of an international nonprofit called the Global Microbiome Conservancy, which aims “to isolate and preserve gut bacterial lineages before they go the way of dodos and dinosaurs.” Despite evidence that species diversity is a reductive metric for the health of the microbiome, Nelson and many others prefer to see the modern bowel as an imperiled wilderness. It’s the same understanding that drives even healthy patients to the clinic hoping to safeguard their guts, and fearing that the damage might already have been done.

In The Anti-Viral Gut, a manual for preventing infection by bolstering gut health, rudimentary intuitions about the gastrointestinal system can be especially powerful. “Just think about where your digestive tract is located,” writes the gastroenterologist and Georgetown University professor Robynne Chutkan, making a case for the gut’s physiological importance. “It’s in the center of your body.” As an interface between the body and the wider world, the gut is the most outward-facing of our internal organs. At once porous and protective, accessible and enigmatic, it inspires speculation.

Unlike Ravella and Nelson, Chutkan has written a few previous books. With titles like Gutbliss and The Microbiome Solution, they are less popular science than self-help, claiming to pull back the curtain on cutting-edge research in the service of personal health. Recognizing this template clarifies how old intuitions get dressed up for new public health events. While masks, social distancing, vaccines, and monoclonal antibodies have emerged as our most effective tools to combat Covid-19, Chutkan writes that “strengthening your immune system by optimizing your gut microbiome is arguably the most effective strategy.” She cites research in which gut microbiota appear to predict the development of severe respiratory symptoms in patients with Covid. These turn out to be pilot studies with small samples, though, further limited by the fact that microbiome sequencing was done after infection, making it difficult to characterize species variation as cause or consequence.

Chutkan returns to the familiar idea of an “immune equilibrium” calibrated by the microbiome, proposing that autoimmune disease and infectious susceptibility result from the scales tipping in either direction. Like Ravella, Chutkan places various items on these scales—bacteria, lymphocytes, sleep deprivation, green juice—without quantifying their relative weights, leaving readers with a general uneasiness about a balance that’s forever teetering.

She offers the microbiome’s complexity as an indicator of its power while at the same time flattening it into binaries, in which certain bacteria represent “virus-busting superstars” and others are “bandits.” Her language is unsubtle, capitalizing on recent fears of viral penetration. The gut is a shield, she writes, but one easily weakened by a compromised microbiome, “creating cracks that allow viruses to seep through, gain access to your internal organs, and run amok in your body.” While this image could lead to the same gloomy chanciness that governs Ravella’s account of inflammation, Chutkan steers readers in the opposite direction, projecting wild confidence in an optimized microbiome’s ability to mitigate health threats present and future, known and unknown.

It’s striking how much credence Ravella, Nelson, and Chutkan give to the research they cite, without critically interrogating each study’s design or methodology. Caveats are offered in general terms—Ravella rightly notes that microbiome research is often limited by “the lack of a reliable reference point,” for instance, since microbial profiles “vary immensely both within and between bodies”—but never in a way that undermines the central thesis. In recounting an early-twentieth-century trend in Western medicine to frame constipation as a postindustrial epidemic, Nelson describes the abiding temptation to overinterpret our own bowel function, “to read the undigested tea leaves, to seek clues about our own mortality floating in a toilet bowl.” But he stops short of observing how that temptation might linger in the present.

Despite the shortcomings of these new visions of the gut, I’m sympathetic to the impulse that drives us toward them. In The Cure Within (2008), a cultural history of mind–body medicine, Anne Harrington suggests that the appeal of psychosomatic disease models might follow from the “existential deficiency” of biomedicine’s strictly physicalist approach. The latter offers intricate explanations for how we get sick but usually fails to answer the question of why. Contemporary models of the gut seem to correct for biomedicine’s shortfalls by a similar logic. They connect our health to the world around us and offer loftier language for crafting stories about disease than what’s typical in Western health care: falling sick is a problem of internal depletion, staying well is a matter of keeping the fire at bay.

We might also be lured in by the feeling of control afforded to us by the microbiome. In the mid-1970s, the social critic Ivan Illich described the “medicalization of life” as a sinister transformation of collective problems like pollution, food insecurity, and exploitative labor practices into scientifically legible, clinically profitable diagnoses. Ravella, Nelson, and Chutkan suggest that the reverse is possible, and that caring for one’s digestive system could also address sociopolitical issues. “Once you understand that you, as the host, are in the driver’s seat when it comes to battling viruses,” Chutkan writes in her instructions on Covid prevention, “the path forward for how to emerge victorious becomes clear.” In the face of the intractable problems that loom over our lives—corporate farming, global warming, zoonotic infections—what a gift it is to have something to do about them, no matter how little sense it makes.