Researchers have identified a toxin from bacteria commonly found in dirty water that kills protective immune cells in the colon, increasing the risk of ulcerative colitis. This discovery, from studies in humans and mice, suggests new treatment possibilities for the inflammatory bowel disease. The findings highlight the role of macrophage-toxic bacteria in triggering the condition.
Ulcerative colitis, one of the two primary forms of inflammatory bowel disease (IBD), involves inflammation of the colon and rectum lining. It features alternating periods of symptom-free phases and flare-ups, with severe cases potentially requiring colon removal. The exact causes remain unclear, often viewed as an autoimmune disorder influenced by environmental and genetic factors.
A team led by Xuena Zhang at Nanjing University in China examined the role of immune cells called macrophages, which regulate inflammation in tissues like the colon. In colon tissue from people with ulcerative colitis, they observed lower levels of these resident macrophages compared to healthy individuals. Experiments in mice showed that depleting macrophages increased susceptibility to colitis, leading to damaged and inflamed colon linings.
Further analysis of faecal samples from ulcerative colitis patients revealed the presence of aerolysin, a toxin highly damaging to macrophages but sparing other gut cells. Aerolysin is produced by certain strains of Aeromonas bacteria, prevalent in fresh and brackish waters, which the researchers term macrophage-toxic bacteria (MTB). Infecting mice with MTB heightened colitis risk, but removing the aerolysin gene from the bacteria or neutralizing the toxin with antibodies prevented this effect.
Aeromonas bacteria appeared in 72 percent of 79 ulcerative colitis patients' stool samples, versus just 12 percent of 480 healthy individuals. However, not all cases involve MTB, and some carriers do not develop the disease.
"We cannot conclude that MTB is the sole cause of ulcerative colitis," Zhang stated. "Persistent MTB infection can induce a hypersensitive state in the colon, but this does not mean that every infected individual will develop colitis. The occurrence of colitis in this context is undoubtedly influenced by environmental and genetic factors."
Zhang proposed three treatment avenues: drugs to neutralize aerolysin, vaccines against the toxin or bacteria, and phage therapy to target MTB. Martin Kriegel at University Hospital Münster in Germany noted, "The case is strong for the MTB toxin disrupting gut immunity by depleting special macrophages in the gut tissue." He added that other unidentified bacteria likely contribute, as germ-free mice infected with MTB alone did not show increased colitis risk.
The team plans broader epidemiological studies to confirm the MTB-ulcerative colitis link, potentially explaining rising IBD rates. The research was published in Science (DOI: 10.1126/science.adz4712).