Gut Microbiota, in the Halfway between Nutrition and Lung Function

Abstract

The gut microbiota is often mentioned as a "forgotten organ" or "metabolic organ", given its profound impact on host physiology, metabolism, immune function and nutrition. A healthy diet is undoubtedly a major contributor for promoting a "good" microbial community that turns out to be crucial for a fine-tuned symbiotic relationship with the host. Both microbial-derived components and produced metabolites elicit the activation of downstream cascades capable to modulate both local and systemic immune responses. A balance between host and gut microbiota is crucial to keep a healthy intestinal barrier and an optimal immune homeostasis, thus contributing to prevent disease occurrence. How dietary habits can impact gut microbiota and, ultimately, host immunity in health and disease has been the subject of intense study, especially with regard to metabolic diseases. Only recently, these links have started to be explored in relation to lung diseases. The objective of this review is to address the current knowledge on how diet affects gut microbiota and how it acts on lung function. As the immune system seems to be the key player in the cross-talk between diet, gut microbiota and the lungs, involved immune interactions are discussed. There are key nutrients that, when present in our diet, help in gut homeostasis and lead to a healthier lifestyle, even ameliorating chronic diseases. Thus, with this review we hope to incite the scientific community interest to use diet as a valuable non-pharmacological addition to lung diseases management. First, we talk about the intestinal microbiota and interactions through the intestinal barrier for a better understanding of the following sections, which are the main focus of this article: the way diet impacts the intestinal microbiota and the immune interactions of the gut-lung axis that can explain the impact of diet, a key modifiable factor influencing the gut microbiota in several lung diseases.

Keywords: diet; gut microbiota; gut-lung axis; immune system; lung function; nutrition respiratory health.

Figure 1

Human gut microbiota: the five major bacterial phyla and their predominant genera, according to the study by Qin et al. 2015 [22,23].

Figure 2

In homeostasis, microbe-associated molecular patterns (MAMPs) from the gut microbiota are recognised by pattern recognition receptors (e.g., Toll-like receptors (TLRs)) and induce antigen presenting cells (APCs), such as macrophages and dendritic cells (DC), to produce interleukins (e.g., IL- 1β and IL-10) to regulate immune responses by different subsets of T cells, neutrophils and macrophages, among others. Activated APCs induce differentiation of naïve CD4⁺ T cells into CD4⁺ regulatory T cells (Treg) (which are crucial for both maintaining tolerance to commensal microbiota and regulating other immune cells), and other effector T cells such as Th1 or Th17 (expressing cytokines, e.g., IL-17 and interferon gamma (IFNγ)) with a central role in host defence against invading pathogens, while controlling the expansion of commensals. Microbial cells or their products in the lamina propria are either phagocytosed and eliminated or transferred to mesenteric lymph nodes (MLN) by APCs, where they induce differentiation of the T and B cells. Activated B and T cells move back (black dashed arrows) to the intestinal mucosa to directly act on their target or to continue to trigger other immune cells. The majority of activated B cells differentiate into immunoglobulin A (IgA)-producing plasma cells. Bacterial metabolites, such as short-chain fatty acids (SCFAs), and expression of antimicrobial peptides (e.g., RegIIIγ) by epithelial cells (induced by TLR activation by MAMPs) reinforce the intestinal barrier integrity. Proposed pathways of the gut–lung axis that would explain the impact of the gut microbiota on the lung immunity include the migration of: (1) activated T and B cells from the MLN to distal sites such as the lung epithelium and lung lymph nodes, through lymph and blood; (2) microbial products and metabolites or surviving bacteria from the intestinal mucosa to the lung, through systemic propagation by lymph and blood circulations. Although not yet well established in the literature, the other way around has been proposed as well (from lung to gut), with the lung microbiota exerting effects in the intestinal mucosa. Scheme based on Bingula et al. [52].