The Gastrointestinal Microbiome: A Review

Abstract

The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune-mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.

Keywords: Metagenomics; Microbiomics; Microbiota; Prebiotics; Probiotics.

Figure 1

Definitions and methods of analysis of the intestinal microbiome. Terminology and technical aspects related to the analysis of microbiomic data can be a barrier to understanding the available literature. The information here is not intended to be a thorough technical overview of the field. Rather, these definitions are meant to familiarize the reader with the fundamental concepts and terminology present in the literature.

Figure 2

Factors influencing gut microbial development and steady states over time. The adult gastrointestinal microbiome is remarkably stable, although several factors influence gut microbial steady states starting at the time of birth. The infant microbiome is derived from maternal and environmental organisms and develops under selective pressure in the gut. Diet, drug administration, and disease states impact the intestinal microbiome, leading to transient or persistent dysbiosis, depending on the nature of the insult and its duration.

Figure 3

Taxonomy and phylogeny of common constituents of the gastrointestinal microbiome. Microbiomic studies rely on taxonomic classification of bacteria based on DNA sequencing analysis. This literature commonly features results in which organisms with similar names but different phylogenetic levels are listed side‐by‐side. This figure was prepared to provide readers with a reference containing the most common organisms found in the gut, along with their phylogenetic relationships. Taxonomic and phylogenetic information courtesy of the NCBI Taxonomy Browser (https://www.ncbi.nlm.nih.gov).

Figure 4

Balance between anti and pro‐inflammatory states in the intestinal mucosa. Mucosal‐microbial homeostasis is a complex and rapidly evolving subject. This simplified diagram is intended to provide examples of some of the most well‐described immunologic interactions between the microbiota and host mucosa. This image represents a schematic cross section of the gut epithelium, mucus layer, and lumen. The colorful rods, ovals, and circles at the top of the image represent luminal microbiota and the blue haze in which some reside is the mucus layer. A. In healthy individuals, pro‐ and anti‐inflammatory signals are balanced such that commensal organisms are recognized and tolerated, while pathogens are prevented from penetrating the mucus layer and underlying epithelium. SCFAs strengthen epithelial tight junctions and stimulate the production of the mucus layer. Commensal organisms are recognized by dendritic cells and specialized epithelial M cells, promoting the maturation of naïve T‐lymphocytes into T_reg cells that secrete anti‐inflammatory and immunomodulatory cytokines. Innate lymphocytes stimulate the overlying epithelial cells to secrete antimicrobial defensins. B. States of dysbiosis are characterized by reduced diversity in the resident microbiota depicted here as an increased relative abundance of yellow rods. Recognition of a shifting antigenic milieu by dendritic cells and M cells results in the maturation of naïve T cells into Th1 and Th17 cells, both of which secrete pro‐inflammatory cytokines. Additionally, altered microbial metabolism (e.g, reduced SCFA production) promotes degradation of host protective factors, such as the mucus layer, that stabilize gut microbial communities and prevent colonization by pathogens.