Next Generation Microbiome Research: Identification of Keystone Species in the Metabolic Regulation of Host-Gut Microbiota Interplay

Abstract

The community of the diverse microorganisms residing in the gastrointestinal tract, known as the gut microbiota, is exceedingly being studied for its impact on health and disease. This community plays a major role in nutrient metabolism, maintenance of the intestinal epithelial barrier but also in local and systemic immunomodulation. A dysbiosis of the gut microbiota, characterized by an unbalanced microbial ecology, often leads to a loss of essential functions that may be associated with proinflammatory conditions. Specifically, some key microbes that are depleted in dysbiotic ecosystems, called keystone species, carry unique functions that are essential for the balance of the microbiota. In this review, we discuss current understanding of reported keystone species and their proposed functions in health. We also elaborate on current and future bioinformatics tools needed to identify missing functions in the gut carried by keystone species. We propose that the identification of such keystone species functions is a major step for the understanding of microbiome dynamics in disease and toward the development of microbiome-based therapeutics.

Identifying keystone species in microbial communities using deep learning

“…Based on the ranking of the median structural keystoneness, we found that among those top-ranking species, many of them have been identified as keystone species that carry unique functions and are essential for the maintaining host-microbe hemeostasis 41 . For example, Bifidobacteria are keystone microorganisms in gut microbiota associated with early life 42 ;…”

“…Prevotella copri is a keystone species of a healthy human intestinal mucosa 43 ; Faecalibacterium prausnitzii is a keystone species that produces butyrate and its reduced abundance has been associated with Crohn's disease 44 ; Bifidobacterium longum is a minority species, but influences gut microbiota formation by breaking down complex carbohydrates and providing degradants for other bacterial groups to use 45 ; Ruminococcus bromii plays key roles in promoting the synergistic utilization of resistant starch (RS) by initiating degradation of insoluble RS particles 5,41 (Fig. 5a).…”

“…Based on the ranking of the median structural keystoneness, we found that among those top-ranking species, many of them have been identified as keystone species that carry unique functions and are essential for the maintaining host-microbe hemeostasis 41 . For example, Bifidobacteria are keystone microorganisms in gut microbiota associated with early life 42 ; Prevotella copri is a keystone species of a healthy human intestinal mucosa 43 ; Faecalibacterium prausnitzii is a keystone species that produces butyrate and its reduced abundance has been associated with Crohn’s disease 44 ; Bifidobacterium longum is a minority species, but influences gut microbiota formation by breaking down complex carbohydrates and providing degradants for other bacterial groups to use 45 ; Ruminococcus bromii plays key roles in promoting the synergistic utilization of resistant starch (RS) by initiating degradation of insoluble RS particles 5, 41 ( Fig.5a ).…”

Role-Playing Between Environmental Pollutants and Human Gut Microbiota: A Complex Bidirectional Interaction

“…The so-called gut microbiome includes the whole genome of the GM, encoding for over 100-fold more genes than the human genome ( 36 ). The recent advent of metagenomics, which combines the next-generation sequencing (NGS) technology with the computational analysis of the 16S ribosomal RNA (rRNA) amplicons, helps in the characterization of both diversity and abundance of the gut microbiome ( 37 ). Metagenomics, together with metatranscriptomics, metaproteomics, and metabolomics, is currently allowing us to understand the impact of each individual bacterial species on the health of the host ( 38 ).…”

How does Quorum Sensing of Intestinal Bacteria Affect Our Health and Mental Status?

“…The importance of AhR cannot be overemphasized as it plays a crucial role in barrier integrity; intestinal and immune homeostasis, mostly due to the regulation of tight junction proteins; the generation and survival of intraepithelial lymphocytes (IELs); the production of IL-22 and IL-10; the regulation of peristalsis and microbiota density; the regulation of goblet cell differentiation in the colon, specifically preventing goblet cell depletion in the elderly [ 2 , 122 , 127 , 137 ]; and the stimulation of antimicrobial peptide production via IL-22 [ 138 , 139 , 140 , 141 , 142 ]. Individuals with IBD and celiac disease have low levels of AhR in their feces [ 133 ].…”