The effects of dietary fiber on a host’s innate immune responses are thought to be mediated at local and systemic levels via short-chain fatty acids (SCFAs). Previous preclinical research has shown that mice that consume a diet high in fermentable fiber are protected against allergic airway inflammation through SCFAs. However, underlying mechanisms are poorly understood.
A new study, led by Prof. Benjamin Marsland from the Department of Immunology and Pathology at Monash University (Melbourne, Australia), has found that the fermentable fiber inulin and short-chain fatty acids exert beneficial effects on the immune system, allowing mice to control influenza infections.
In order to explore the role of fermentable dietary fiber on antiviral immunity, mice were born and raised on a low-fiber diet supplemented with either inulin (high fiber group) or cellulose (control group). Then, the mice were exposed to the influenza A virus via the intranasal route. The mice fed a high fiber diet showed prolonged survival, an improved clinical score and enhanced lung elasticity with better lung function. Furthermore, high-fiber diet-fed mice were protected against influenza-induced tissue destruction and lethality, supported by decreased myeloperoxidase activity, which contributes to inflammatory lung damage. These results show the protective effect of dietary fiber against influenza-induced immunopathology.
Inulin supplementation led to a marked alteration of gut microbiota composition, with an increase in the proportion of Bacteroidaceae together with a reduction in operational taxonomic units belonging to the Firmicutes phylum. Although the high-fiber diet led to significantly different microbial communities, it did not alter gut microbiota richness or diversity when compared with the control group. Furthermore, the high-fiber diet led to a strong increase in butyrate both in the feces and the serum.
Immune response following a sublethal influenza infection was also assessed to elucidate the mechanisms involved in the beneficial effects of the high-fiber diet. The researchers found that inulin increased survival of influenza-infected mice via two complementary mechanisms. First, dietary fiber prevented neutrophil influx into the airways in a SCFA- and free fatty acid receptor 3 (FFAR3)-dependent manner by decreasing the levels of the chemokine (C-X-C motif) ligand 1 (CXCL1) produced by lung monocytes and macrophages. This, in turn, reduced early neutrophil infiltration into the airways and avoided increased tissue damage. Specifically, the high-fiber diet also led to reduced airway neutrophilia by altering hematopoiesis and promoting the differentiation of alternatively activated macrophages from monocytes with an anti-inflammatory phenotype (named Ly6c– patrolling monocytes) in the lungs of influenza-infected mice, producing less CXCL1 and avoiding tissue damage. The increase in Ly6c– patrolling monocytes that give rise to monocytes with an anti-inflammatory profile in influenza-infected mice’s lungs suggests that the effect of dietary fiber and SCFAs on bone marrow hematopoiesis depended on the niche context. In this regard, a previous study with mice also showed that an innate immune response is involved in protecting the host against influenza infection through type I interferon signaling via a phagocytic-dependent mechanism.
Meanwhile, diet-derived SCFAs boosted CD8+ T cell effector function by enhancing cellular metabolism via FFAR3 and fatty acid oxidation and increasing viral clearance.
In conclusion, this experimental study shows the role of dietary fermentable fiber and SCFAs in modulating host immune response against influenza infection. Beyond their well-known anti-inflammatory properties, SCFAs may also act by shaping monocyte hematopoiesis and CD8+ T cell metabolism. The role of dietary fiber in the development of protective immunity and reduced immune-mediated pathology with regards to the influenza infection deserves further research, in order to elucidate whether SCFAs may be involved in preventing and treating viral infections.
Trompette A, Gollwitzer ES, Pattaroni C, et al. Dietary fiber confers protection against flu by shaping Ly6c– patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity. 2018; 48:1-14. doi: 10.1016/j.immuni.2018.04.022.