Selective Manipulation of the Gut Microbiota Improves Immune Status in Vertebrates

Abstract

All animals develop in association with complex microbial communities. It is now well established that commensal microbiota is essential for the correct functionality of each organ in the host. Particularly, the commensal gastro-intestinal microbiota (CGIM) is a key factor for development, immunity and nutrient conversion, rendering them bio-available for various uses. Thus, nutritional inputs generate a positive loop in maintaining host health and are essential in shaping the composition of the CGIM communities. Probiotics, which are live exogenous microorganisms, selectively provided to the host, are a promising concept for manipulating the microbiota and thus for increasing the host health status. Nevertheless, most mechanisms induced by probiotics to fortify the immune system are still a matter of debate. Alternatively, prebiotics, which are non-digestible food ingredients, can favor the growth of specific target groups of CGIM. Several metabolites are produced by the CGIM, one of the most important are the short-chain fatty acids (SCFAs), which emerge from the fermentation of complex carbohydrates. SCFAs have been recognized as key players in triggering beneficial effects elicited by simple diffusion and by specific receptors present, thus, far only in epithelial cells of higher vertebrates at different gastro-intestinal locations. However, both strategies have shown to provide resistance against pathogens during periods of high stress. In fish, knowledge about the action of pro- and prebiotics and SCFAs is still limited. Thus, in this review, we briefly summarize the mechanisms described on this topic for higher vertebrates and discuss why many of them may operate in the fish gut representing a model for different mucosal tissues.

Keywords: SCFA; fish; host–microbe; humans; immunity; microbiota; prebiotics; probiotics; vertebrates.

Figure 1

Potential microbial strategies to improve gut mucosal immunity in fish. The therapeutic approach mechanisms include: (A) competitive exclusion for binding sites and translocation, (B) enhanced barrier function by reversing the increased intestinal permeability, (C) enhanced mucosal immunoglobulin IgT/Z response to enteral antigens, (D) reduction of secretion of inflammatory mediators, (E) stimulation of innate immune functions, (F) stimulate the release of antimicrobial peptides (AMPs) at the mucosal layer, and (G) enhanced availability of anti-inflammatory mediators by regulatory immune cells. (H) Production of metabolic health-enhancers like SCFAs by non-digestible prebiotics, (I) diffusion of SCFAs through the enterocytes to improve mucosa barrier functions. (J) Probiotics have been suggested to confer several health benefits on the host. However, their mechanisms of action are not well understood. (K) Synbiotics are a mix of pre- and probiotics, thus their mode of action are much more difficult to define.

Figure 2

Host-microbial load under health and dysbiosis. Addition in diet of exogenous microbial sources may increase fish health through a host–microbe positive loop. Commensal gut microbes might be modulated by dietary administration of target microbes, non-digestible elements, or a mix of both. Expected output should turn in preventive or curative strategies. The use of pro-, pre-, and/or synbiotics is expected to restore the homeostatic stage. Assessment of the selected approach might be quantified, modeled, or dissected using omics tools, germ-free models, and microbiome analyses.