Common Types of Inflammatory Bowel Disease Linked to Harmful Bacteria

Toxins from bacteria in contaminated water can destroy immune cells in the colon’s lining. This implies that individuals whose intestines host these bacteria are significantly more likely to develop ulcerative colitis.

This conclusion is derived from a series of studies undertaken with both humans and animals by Shwena Chan and colleagues at Nanjing University, China. If validated, these findings could pave the way for new treatment options.

Ulcerative colitis is one of the primary types of inflammatory bowel disease (IBD), marked by inflammation of the colon and rectum lining. Symptoms typically fluctuate between periods of remission and flare-ups, sometimes necessitating the removal of the colon in severe cases.

The exact cause of ulcerative colitis remains unclear, although it is often regarded as an autoimmune disorder influenced by both genetic and environmental factors. Chan’s team theorized that immune cells called macrophages might be integral to the condition.

Macrophages are found throughout various body tissues, performing the dual roles of clearing debris and bacteria while regulating local immune responses. They can signal additional immune cell recruitment and initiate inflammation but are equally important in mitigating it.

Researchers discovered that the density of resident macrophage cells was notably reduced in colon tissue from patients with ulcerative colitis compared to those without the condition. Further experimentation demonstrated that depleting macrophages in mice increased their susceptibility to colitis, suggesting that losing macrophage protection leads to colon damage and inflammation.

But what accounts for the lower macrophage levels in ulcerative colitis patients? By analyzing fecal samples, the research team identified a toxin named aerolysin, which significantly harms macrophages while sparing other intestinal cells.

Aerolysin is secreted by several strains of bacteria belonging to the genus Aeromonas, frequently found in freshwater and brackish environments. The strains responsible for producing aerolysin are referred to as MTB (macrophage-toxic bacteria).

In experiments where mice were deliberately infected with MTB, they exhibited greater vulnerability to colitis. Conversely, even after removing the aerolysin gene from the bacteria or neutralizing the toxin with antibodies, the mice did not show increased susceptibilities to the condition.

Ultimately, the research team tested for Aeromonas in stool samples, discovering its presence in 72% of the 79 patients with ulcerative colitis, versus only 12% among 480 individuals without the condition. This test, however, could not confirm if these bacteria were indeed MTB or if they produced aerolysin.

The findings offer a nuanced perspective. Not every case of ulcerative colitis is linked to MTB, and some individuals can carry MTB without developing the disease.

“We cannot assert that MTB is the exclusive cause of ulcerative colitis,” Zhang states. “Ongoing MTB infection can create a hypersensitive environment in the colon, yet not everyone infected will develop colitis.”

“Environmental and genetic factors certainly influence the emergence of colitis,” she adds.

According to Zhang, there are at least three potential approaches for new treatment development. One involves creating drugs to neutralize the toxin; another would focus on vaccines targeting the toxin or the bacteria producing it; while a third approach seeks to eradicate toxin-producing bacteria via phage therapy, which utilizes viruses that selectively kill specific bacteria.

“The leading theory posits that MTB toxin depletes specialized macrophages in the intestinal lining, undermining intestinal immunity,” explains Dr. Martin Kriegel from the University Hospital of Münster, Germany.

He has observed that when the team eradicated all intestinal bacteria in mice and subsequently infected them with MTB, their susceptibility to colitis diminished. This observation indicates that other yet-to-be-identified bacterial species could also play a role.

“Nonetheless, this may represent a crucial, overlooked factor in the multi-step development of ulcerative colitis, especially in China,” Kriegel suggests.

Zhang and her research group intend to conduct more extensive epidemiological studies to substantiate the association between MTB and ulcerative colitis. If MTB infection is confirmed and becomes increasingly prevalent, it may elucidate the rising incidence of IBD.