Immune system plays role in regulating gut bacteria and inflammation, says new animal study

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A new study published in the journal Nature Communications¹ showed that the immune system helps maintain good gut bacteria in addition to defending against bad bacteria. Researchers found that the increased presence of a protein called NLRP1, which is responsible for sensing infection, was correlated with fewer good bacteria and anti-inflammatory molecules in the gut, leading to higher levels of inflammation. This may provide some clue to the underlying cause of inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis.

Researchers used mice with deficient levels of NLRP1 and then induced colitis. For comparison, mice with higher expression of NLRP1 were also induced with colitis. Results showed that lower levels of NLRP1 correlated with protective effects against colitis, indicated by reduced weight loss, sustained colon length, and lower histology scores. There was also less severe inflammation in NLRP1-deficient mice-specifically, lower levels of the proinflammatory cytokine IL-18.

“Too much NLRP1 leads to an overproduction of a signaling molecule called IL-18 that tells the body to mount a protective response against the threat of colonization by bad bacteria-but as a consequence the good bacteria and their anti-inflammatory products are also lost,” explains Associate Professor Seth Masters, one of the lead researchers, in a press release. “Inflammation occurs as part of this process, so when too much IL-18 is produced, inflammation can continue unchecked and cause significant damage to the gastrointestinal tract.”

Researchers also found that the presence of good bacteria produces a molecule called butyrate, which is important to keeping levels of inflammation down. NLRP1-deficient mice in the study had increased butyrate production. “While we don't know exactly what the genetic, microbial, or environmental triggers for NLRP1 are, it is clear that faulty regulation of NLRP1 is an underlying cause of IBD,” said Masters. “By stopping overproduction of NLRP1 or IL-18 in patients with IBD, we may be able boost the number of good bacteria and anti-inflammatory properties in the gut and help to prevent or fight the damaging effects of too much inflammation.”
 

References:

1. Tye H et al. “NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease.” Nature Communications, vol. 9 (2018): 3728