Medscape Medical News
Marta Zaraska
June 10, 2024
When doctors and patients consider the appendix, it’s often with urgency. In cases of appendicitis, the clock could be ticking down to a life-threatening burst. Thus, despite recent research suggesting antibiotics could be an alternative therapy, appendectomy remains standard for uncomplicated appendicitis.
But what if removing the appendix could raise the risk for gastrointestinal (GI) diseases like irritable bowel syndrome and colorectal cancer? That’s what some emerging science suggests. And though the research is early and mixed, it’s enough to give some health professionals pause .
“If there’s no reason to remove the appendix, then it’s better to have one,” said Heather Smith, PhD, a comparative anatomist at Midwestern University, Glendale, Arizona. Preemptive removal is not supported by the evidence, she said.
To be fair, we’ve come a long way since 1928, when American physician Miles Breuer suggested that people with infected appendixes should be left to perish, so as to remove their inferior DNA from the gene pool (he called such people “uncivilized” and “candidates for extinction”). Darwin, while less radical, believed the appendix was at best useless — a mere vestige of our ancestors switching diets from leaves to fruits.
What we know now is that the appendix isn’t just a troublesome piece of worthless flesh. Instead, it may act as a safe house for friendly gut bacteria and a training camp for the immune system. It also appears to play a role in several medical conditions, from ulcerative colitis and colorectal cancer to Parkinson’s disease and lupus. The roughly 300,000 Americans who undergo appendectomy each year should be made aware of this, some experts say. But the frustrating truth is, scientists are still trying to figure out in which cases having an appendix is protective and in which we may be better off without it.
A “Worm” as Intestinal Protection
The appendix is a blind pouch (meaning its ending is closed off) that extends from the large intestine. Not all mammals have one; it’s been found in several species of primates and rodents, as well as in rabbits, wombats, and Florida manatees, among others (dogs and cats don’t have it). While a human appendix “looks like a little worm,” Smith said, these anatomical structures come in various sizes and shapes. Some are thick, as in a beaver, while others are long and spiraling, like a rabbit’s.
Comparative anatomy studies reveal that the appendix has evolved independently at least 29 times throughout mammalian evolution. This suggests that “it has some kind of an adaptive function,” Smith said. When French scientists analyzed data from 258 species of mammals, they discovered that those that possess an appendix live longer than those without one. A possible explanation, the researchers wrote, may lie with the appendix’s role in preventing diarrhea.
Their 2023 study supported this hypothesis. Based on veterinary records of 45 different species of primates housed in a French zoo, the scientists established that primates with appendixes are far less likely to suffer severe diarrhea than those that don’t possess this organ. The appendix, it appears, might be our tiny weapon against bowel troubles.
For immunologist William Parker, PhD, a visiting scholar at the University of North Carolina at Chapel Hill, these data are “about as good as we could hope for” in support of the idea that the appendix might protect mammals from GI problems. An experiment on humans would be unethical, Parker said. But observational studies offer clues.
One study showed that compared with people with an intact appendix, young adults with a history of appendectomy have more than double the risk of developing a serious infection with non-typhoidal Salmonella of the kind that would require hospitalization.
A “Safe House” for Bacteria
Such studies add weight to a theory that Parker and his colleagues developed back in 2007: That the appendix acts as a “safe house” for beneficial gut bacteria.
Think of the colon as a wide pipe, Parker said, that may become contaminated with a pathogen such as Salmonella. Diarrhea follows, and the pipe gets repeatedly flushed, wiping everything clean, including your friendly gut microbiome. Luckily, “you’ve got this little offshoot of that pipe,” where the flow can’t really get in “because it’s so constricted,” Parker said. The friendly gut microbes can survive inside the appendix and repopulate the colon once diarrhea is over. Parker and his colleagues found that the human appendix contains a thick layer of beneficial bacteria. “They were right where we predicted they would be,” he said.
This safe house hypothesis could explain why the gut microbiome may be different in people who no longer have an appendix. In one small study, people who’d had an appendectomy had a less diverse microbiome, with a lower abundance of beneficial strains such as Butyricicoccus and Barnesiella, than did those with intact appendixes.
The appendix likely has a second function, too, Smith said: It may serve as a training camp for the immune system. “When there is an invading pathogen in the gut, it helps the GI system to mount the immune response,” she said. The human appendix is rich in special cells known as M cells. These act as scouts, detecting and capturing invasive bacteria and viruses and presenting them to the body’s defense team, such as the T lymphocytes.
If the appendix shelters beneficial bacteria and boosts immune response, that may explain its links to various diseases. According to an epidemiological study from Taiwan,patients who underwent an appendectomy have a 46% higher risk of developing irritable bowel syndrome (IBS) — a disease associated with a low abundance of Butyricicoccus bacteria. This is why, the study authors wrote, doctors should pay careful attention to people who’ve had their appendixes removed, monitoring them for potential symptoms of IBS.
The same database helped uncover other connections between appendectomy and disease. For one, there was type 2 diabetes: Within 3 years of the surgery, patients under 30 had double the risk of developing this disorder. Then there was lupus: While those who underwent appendectomy generally had higher risk for this autoimmune disease, women were particularly affected.
The Contentious Connections
The most heated scientific discussion surrounds the links between the appendix and conditions such as Parkinson’s disease, ulcerative colitis, and colorectal cancer. A small 2019 study showed, for example, that appendectomy may improve symptoms of certain forms of ulcerative colitis that don’t respond to standard medical treatments. A third of patients improved after their appendix was removed, and 17% fully recovered.
Why? According to Parker, appendectomy may work for ulcerative colitis because it’s “a way of suppressing the immune system, especially in the lower intestinal areas.” A 2023 meta-analysis found that people who’d had their appendix removed before being diagnosed with ulcerative colitis were less likely to need their colon removed later on.
Such a procedure may have a serious side effect, however: Colorectal cancer. French scientists discovered that removing the appendix may reduce the numbers of certain immune cells called CD3+ and CD8+ T cells, causing a weakened immune surveillance. As a result, tumor cells might escape detection.
Yet the links between appendix removal and cancer are far from clear. A recent meta-analysis found that while people with appendectomies generally had a higher risk for colorectal cancer, for Europeans, these effects were insignificant. In fact, removal of the appendix actually protected European women from this particular form of cancer. For Parker, such mixed results may stem from the fact that treatments and populations vary widely. The issue “may depend on complex social and medical factors,” Parker said.
Things also appear complicated with Parkinson’s disease — another condition linked to the appendix. A large epidemiological study showed that appendectomy is associated with a lower risk for Parkinson’s disease and a delayed age of Parkinson’s onset. It also found that a normal appendix contains α-synuclein, a protein that may accumulate in the brain and contribute to the development of Parkinson’s. “Although α-synuclein is toxic when in the brain, it appears to be quite normal when present in the appendix,” said Luis Vitetta, PhD, MD, a clinical epidemiologist at the University of Sydney, Camperdown, Australia. Yet, not all studies find that removing the appendix lowers the risk for Parkinson’s. In fact, some show the opposite results.
How Should Doctors View the Appendix?
Even with these mysteries and contradictions, Vitetta said, a healthy appendix in a healthy body appears to be protective. This is why, he said, when someone is diagnosed with appendicitis, careful assessment is essential before surgery is performed.
“Perhaps an antibiotic can actually help fix it,” he said. A 2020 study published in The New England Journal of Medicine showed that antibiotics may indeed be a good alternative to surgery for the treatment of appendicitis. “We don’t want necessarily to remove an appendix that could be beneficial,” Smith said.
The many links between the appendix and various diseases mean that doctors should be more vigilant when treating patients who’ve had this organ removed, Parker said. “When a patient loses an appendix, depending on their environment, there may be effects on infection and cancer. So they might need more regular checkups,” he said. This could include monitoring for IBS and colorectal cancer.
What’s more, Parker believes that research on the appendix puts even more emphasis on the need to protect the gut microbiome — such as taking probiotics with antibiotics. And while we are still a long way from understanding how exactly this worm-like structure affects various diseases, one thing appears quite certain: The appendix is not useless. “If Darwin had the information that we have, he would not have drawn these conclusions,” Parker said.
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