Dietary Fiber Drives IL-1β-Dependent Peritonitis Induced by Bacteroides fragilis via Activation of the NLRP3 Inflammasome.

Abstract

Intestinal barrier is essential for dietary products and microbiota compartmentalization and therefore gut homeostasis. When this barrier is broken, cecal content overflows into the peritoneal cavity, leading to local and systemic robust inflammatory response, characterizing peritonitis and sepsis. It has been shown that IL-1β contributes with inflammatory storm during peritonitis and sepsis and its inhibition has beneficial effects to the host. Therefore, we investigated the mechanisms underlying IL-1β secretion using a widely adopted murine model of experimental peritonitis. The combined injection of sterile cecal content (SCC) and the gut commensal bacteria Bacteroides fragilis leads to IL-1β-dependent peritonitis, which was mitigated in mice deficient in NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome components. Typically acting as a damage signal, SCC, but not B. fragilis, activates canonical pathway of NLRP3 promoting IL-1β secretion in vitro and in vivo. Strikingly, absence of fiber in the SCC drastically reduces IL-1β production, whereas high-fiber SCC conversely increases this response in an NLRP3-dependent manner. In addition, NLRP3 was also required for IL-1β production induced by purified dietary fiber in primed macrophages. Extending to the in vivo context, IL-1β-dependent peritonitis was worsened in mice injected with B. fragilis and high-fiber SCC, whereas zero-fiber SCC ameliorates the pathology. Corroborating with the proinflammatory role of dietary fiber, IL-1R-deficient mice were protected from peritonitis induced by B. fragilis and particulate bran. Overall, our study highlights a function, previously unknown, for dietary fibers in fueling peritonitis through NLRP3 activation and IL-1β secretion outside the gut.

• Authors: Bruno Jennings-Almeida, Juliana P Castelpoggi, Erivan S Ramos-Junior, Eliane de Oliveira Ferreira, Regina M C P Domingues, Juliana Echevarria-Lima, Robson Coutinho-Silva, Aline C A Moreira-Souza, Eliana Mariño, Charles R Mackay, Dario S Zamboni, Maria Bellio, Julio Scharfstein, Leandro A Lobo, Ana Carolina Oliveira
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 206 Issue 10 Pg. 2441-2452 (05 15 2021) ISSN: 1550-6606 [Electronic] United States
• PMID: 33941658 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 by The American Association of Immunologists, Inc.

Chemical References

• Dietary Fiber
• IL1B protein, mouse
• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Receptors, Interleukin-1

Topics

• Animals
• Bacteroides Infections (immunology, microbiology)
• Bacteroides fragilis (immunology)
• Diet
• Dietary Fiber (administration & dosage, adverse effects)
• Disease Models, Animal
• Inflammasomes (metabolism)
• Interleukin-1beta (metabolism)
• Macrophages (immunology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NLR Family, Pyrin Domain-Containing 3 Protein (deficiency, genetics)
• Peritonitis (immunology, microbiology)
• Receptors, Interleukin-1 (deficiency, genetics)
• Signal Transduction (drug effects, immunology)