What causes IBS pain? Maybe immune flare-ups

doi:10.1126/science.371.6527.333

GSTDTAP > 气候变化

DOI	10.1126/science.371.6527.333
	What causes IBS pain? Maybe immune flare-ups
	Jennifer Couzin-Frankel
	2021-01-22
发表期刊	Science
出版年	2021
英文摘要	For millions of people with irritable bowel syndrome (IBS), the condition's cramping, diarrhea, and constipation are frustrating and distressing. And it's made worse when doctors sometimes dismiss the symptoms as “all in the mind or between the ears,” says Guy Boeckxstaens, a gastroenterologist at KU Leuven. Boeckxstaens rejects that view. For years he's sought to understand one hallmark of IBS, abdominal pain brought on by eating. Last week, he and more than 40 colleagues presented data to support a new hypothesis: that this pain is caused by a kind of localized allergic reaction to food. “The idea that you can have a specific allergic response going on in the gut” is “a really new concept,” says Robin Spiller, a gastroenterologist at the University of Nottingham who was not involved in the study and finds it persuasive. An early clue to IBS pain emerged about 15 years ago. Researchers found that in IBS patients, “the immune system was different,” says Giovanni Barbara, a gastroenterologist at the University of Bologna who led the work. In biopsies of intestinal tissue, immune cells called mast cells were activated. Normally, mast cells act as an alert system, spewing out chemicals such as histamine when threatened with infection or other dangers, like parasites. But these IBS patients had no apparent infections, yet their mast cells were activated and caused nearby nerve cells to fire excessively. Barbara recalls that “nobody believed me.” Doubts that IBS pain was rooted in gut biology ran deep. Boeckxstaens, however, was intrigued and went looking for more evidence. Intestinal infections, ranging from acute food poisoning to mild illness, are followed by IBS in about 10% of previously healthy people, and some researchers thought low-grade inflammation persisting in the gut after infection might be the trigger. Yet when Boeckxstaens examined intestinal biopsies of IBS patients, he didn't find inflammation. Instead, he thought a gut infection may disrupt how the organ tolerates protein fragments called antigens, which many foods contain. When battling an infection, the intestine's immune cells may mistake food antigens for enemy forces. A gut reaction to food antigens that persists after infection could explain the pain and cramping that often accompany a meal. To test the idea, Boeckxstaens and colleagues infected mice with harmful gut bacteria, and at the same time fed them antigens from egg whites. After the gut infection cleared, the mice ingested the antigens again—and this time, they seemed to experience abdominal pain, as measured by stomach muscle contractions. Mice that didn't get egg white protein while they were infected had no trouble. Probing further, the researchers found that after an infection, the egg white protein set off a chain reaction similar to what happens in food allergies. The protein anchored itself to antibodies called immunoglobulin E (IgE), which are bound to mast cells. In the mice—as in people with allergies—mast cells then became activated and released their chemicals. The reaction to egg protein endured for at least 4 weeks after the infection. The persistent reaction underscored what Barbara had observed years earlier in people: If mast cells were shooting out chemicals, neurons could become hypersensitive and more excitable, which the body would interpret as pain. These new findings could “open people's minds” to the idea that IBS pain is rooted in biology, says Bana Jabri, a pediatric gastroenterologist and mucosal immunologist at the University of Chicago. Jabri has pursued a similar idea with celiac disease, in which patients can't tolerate gluten, reporting with colleagues in 2019 that ingesting gluten causes a strong immune reaction specific to that substance; the reaction in turn drives abdominal symptoms such as pain and nausea. To find out whether the mouse results applied to patients, Boeckxstaens's group tested 12 people with IBS for four common food allergies: to cow's milk, gluten, wheat, and soy. All were negative. That didn't surprise him: What his mice experienced isn't a classic food allergy, because the animals' immune reaction was localized to the gut. But when the researchers injected these potential allergens rectally, every volunteer had a localized reaction to at least one of the antigens. In a control group of eight healthy people, only two had a borderline gut reaction to either soy or gluten, the researchers reported last week in Nature . (Boeckxstaens suspects some unaffected people may have mild reactions, which their gut can tolerate.) “It's pretty novel and thought-provoking,” says Dan Mucida, an immunologist at Rockefeller University. If the mice's localized IgE reaction holds up in people with IBS, he wonders whether a range of foods can trigger it, or only a few. Another line of inquiry involves treatment. Currently, IBS treatments focus on managing symptoms, but if mast cells and IgE are driving them, at least in some cases, immune therapies could prove useful. Finally, Mucida wonders whether this immune reaction plays a role in cases of IBS induced by triggers other than infection, such as stress. Boeckxstaens is exploring that question now, studying whether in mice, stress alone can induce a similar immune cascade in the gut.
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/312340
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Jennifer Couzin-Frankel. What causes IBS pain? Maybe immune flare-ups[J]. Science,2021.
APA	Jennifer Couzin-Frankel.(2021).What causes IBS pain? Maybe immune flare-ups.Science.
MLA	Jennifer Couzin-Frankel."What causes IBS pain? Maybe immune flare-ups".Science (2021).