To engraft or not to engraft: an ecological framework for gut microbiome modulation with live microbes

Abstract

Strategies aimed at modulating the gut microbiota by using live microbes range from single strains (probiotics or live biotherapeutics) to whole non-defined fecal transplants. Although often clinically efficacious, our understanding on how microbial-based strategies modulate gut microbiome composition and function is vastly incomplete. In this review, we present a framework based on ecological theory that provides mechanistic explanations for the findings obtained in studies that attempted to modulate the gut microbiota of humans and animals using live microbes. We argue that an ecological perspective grounded in theory is necessary to interpret and predict the impact of microbiome-modulating strategies and thus advance our ability to develop improved and targeted approaches with enhanced therapeutic efficiency.

Figure 1

Successful invasion of a microorganism conceptualized as a 4-stage process. (A) The microbe needs to be introduced in sufficient numbers and in an active form, and possess the traits to withstand the pressures of the gut environment. (B) Habitat filters will select for microbes that possess the traits necessary to overcome them, while the host specifically selects for symbionts by a variety of mechanisms (glycans, epithelial capture, etc.). (C) The microbe needs to compete with resident members to access resources to grow and persist in an ecological niche. (D) Successful occupation of niches may result in metabolic activities and/or competitive or synergistic interactions that impacts the resident community’s composition and/or function. Adopted from Mallon et al. 2015 [13*].

Figure 2

Ecological framework describing the characteristics, mechanisms and principles that influence colonization success of microorganisms used in microbiome-modulating strategies. (C) Characteristics of the potential colonists, dose, frequency of entry, activity, as well as the diversity of the propagule population increase the likelihood of colonization success. In addition, traits to overcome habitat filters, engage in symbiotic interactions with the host, and secure resources are essential for engraftment. (H) Host-related mechanisms select for microbes that possess traits to colonize the gut. Habitat filters such as bile acids, defensins, and immune responses select for organisms that possess the necessary adaptation. Host-derived glycans and the provision of adhesion sites can facilitate the establishment of microbes. (M) Microbiome-related mechanisms, mainly related to competition and microbe-microbe interactions define successful engraftment. All three components have to be compliant for engraftment to occur, and components of C, H, and M interact.