Diet–Microbiota Interplay: An Emerging Player in Macrophage Plasticity and Intestinal Health

Abstract

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract with an increasing prevalence worldwide. Targeted therapies for IBD are limited by several factors, including the therapeutic ceiling and the high incidence of non-responders or loss-of-response. In order to improve therapeutic efficacy, there is critical need to decipher disease pathogenesis, currently not well understood. Macrophages, innate immune cells that exhibit high plasticity, perpetuate inflammatory signalling in IBD through excessive release of inflammatory mediators. In recent years, pioneering research has revealed the importance of the interplay between macrophages and gut microbiota in maintaining intestinal homeostasis. Particular attention is focusing on microbiota-derived metabolites, believed to possess immunomodulatory properties capable of manipulating macrophage plasticity. Microbiota-derived short-chain fatty acids (SCFAs) and indole compounds, along with dietary sourced omega-3 (ω-3) polyunsaturated fatty acids (PUFA), exert anti-inflammatory effects, attributable to interactions with macrophages. Before we can effectively incorporate these metabolites into IBD therapies, a deeper understanding of microbiota–macrophage interactions at a molecular level is necessary. Therefore, the aim of this review is firstly to detail current knowledge regarding how diet and microbiota-derived metabolites modify macrophage plasticity. Later, we discuss the concept of therapeutic strategies directed at microbiota–macrophage interactions, which could be highly valuable for IBD therapies in the future.

Gut Microbiome in Inflammatory Bowel Disease: Role in Pathogenesis, Dietary Modulation, and Colitis-Associated Colon Cancer

“…As previously mentioned, the production of SCFAs from fiber in gut microbiota has been established as a protective agent against IBD in recent years [ 66 ]. The most-studied SCFAs (butyrate, acetate, and propionate) exert anti-inflammatory effects in IBD by inhibiting NF-ĸB activation to suppress cytokines [ 66 ].…”

“…As previously mentioned, the production of SCFAs from fiber in gut microbiota has been established as a protective agent against IBD in recent years [ 66 ]. The most-studied SCFAs (butyrate, acetate, and propionate) exert anti-inflammatory effects in IBD by inhibiting NF-ĸB activation to suppress cytokines [ 66 ]. Butyrate, produced by the microbe Firmicutes, exists at highest concentrations in the colon and cecum, and propionate and acetate are byproducts from Bacteroidetes in the small and large intestines.…”

“…Butyrate, produced by the microbe Firmicutes, exists at highest concentrations in the colon and cecum, and propionate and acetate are byproducts from Bacteroidetes in the small and large intestines. SCFA production from fiber is crucial for reducing the inflammatory response in patients with IBD; therefore, a diet rich in fiber is essential to gut health [ 66 ].…”

“…Studies have found ω3FAs to support anti-inflammatory processes when interacting with microbes and alter microbiota diversity, increase beneficial bacteria, and reduce harmful bacteria. ω3FAs encourage growth of SCFA-producing microbes, including the Lachnospiraceae, and lessen the abundance of pathogenic microbes, such as Enterobacteriaceae, in infants [ 66 ]. However, the exact pathways and interactions between ω3FAs and the microbes themselves remain unclear.…”

“…It should, however, be noted that while KD alleviated the progression of intestinal inflammation, it also reduced the abundance of some healthy bacteria, such as Lactobacillus, compared with a normal diet [65]. Fiber in fruits and vegetables has been shown to provide several benefits to patients with IBD, such as prolonging remission and reducing lesions in the intestinal mucosa, while an imbalance in the consumption of fiber is a risk factor for IBD development [66]. Furthermore, a diet rich in oats prevents the worsening of gastrointestinal symptoms in UC, while a diet rich in high-fiber legumes mitigates intestinal inflammation in rodent models of IBD [66].…”