Microbiome-based interventions to modulate gut ecology and the immune system

Abstract

The gut microbiome lies at the intersection between the environment and the host, with the ability to modify host responses to disease-relevant exposures and stimuli. This is evident in how enteric microbes interact with the immune system, e.g., supporting immune maturation in early life, affecting drug efficacy via modulation of immune responses, or influencing development of immune cell populations and their mediators. Many factors modulate gut ecosystem dynamics during daily life and we are just beginning to realise the therapeutic and prophylactic potential of microbiome-based interventions. These approaches vary in application, goal, and mechanisms of action. Some modify the entire community, such as nutritional approaches or faecal microbiota transplantation, while others, such as phage therapy, probiotics, and prebiotics, target specific taxa or strains. In this review, we assessed the experimental evidence for microbiome-based interventions, with a particular focus on their clinical relevance, ecological effects, and modulation of the immune system.

Fig. 1. Constituents and mechanisms of microbiome-based interventions.

a Common constituents of microbiome-based intervention methods are broadly illustrated. b Schematic of the three major categories by which interventions influence the gut microbiome. The simplified native microbiome members are coloured shades of red to purple, while introduced species are shades of blue and prebiotic fibres are green. FMT faecal microbiota transplant, FFT faecal filtrate transplant.

Fig. 2. Visualisation of some discussed mechanisms of how microbiome-based interventions can modulate the immune system.

Each interaction is numbered based on the sub-section they are detailed in. The key mediators and molecules involved are detailed below the scheme. Species known to conduct these interactions are given as examples in black. The mucus layer is depicted in green. As a schematic, the sizes and location of mediators and microbes have been modified to enhance visualisation.