September 17, 2019

A new understanding of microbial processes is helping to reveal the cause of ulcerative colitis through the study of a nonhuman primate disorder, idiopathic chronic diarrhea (ICD).

ICD affects 3 to 5 percent of all captive macaque monkeys, and researchers believe wild macaques could be affected at similar rates. ICD is unresponsive to medical intervention and not caused by any particular pathogens.

California National Primate Research Center (CNPRC) scientist Amir Ardeshir, PhD, first began investigating the relationship between microbiomes and intestinal diseases like ICD in macaques—and ulcerative colitis in humans—when he learned of a human patient who had temporarily treated their ulcerative colitis by consuming the eggs of a parasite called Trichuris trichiura.

Ardeshir tried this patient’s home remedy in ICD-affected monkeys and discovered, astonishingly, that the parasite was an effective treatment in four out of five monkeys.

Now, in his latest study, Ardeshir and a team of researchers have found an interesting relationship between the Trichuris parasite and the monkeys’ microbiome—the community of trillions of microbes living on and in primates’ bodies.

The study found that treated monkeys had different microbial communities than healthy control subjects, making them particularly good at building the protective mucosal layer along the intestinal wall. This layer is key in protecting intestinal epithelium from pathogens.

The team of scientists then identified some of the specific bacteria occurring in cases of ICD using a new software called SAMSA2. This software-based approach revealed not only which bacteria were present in each monkey’s gut, but also provided information about what those bacteria were doing and how they might be interacting.

The researchers found a dramatically high number of “bacteria that are very notorious for mucin degradation,” Ardeshir noted. Mucins are glycoproteins which are necessary for the maintenance of the mucosal layer lining human and nonhuman primate intestines. Without it, the mucosal layer and gut bacteria can’t maintain a healthy relationship. Biopsies of human patients with ulcerative colitis show dysfunctional mucosal layers, suggesting this may be the source of irritation and inflammation in both ICD and ulcerative colitis.

Though the exact causes are still unclear, Ardeshir noted that this study brings the field much closer to a full understanding of these types of intestinal bacterial diseases.

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