Recent Advances in Understanding the Structure and Function of the Human Microbiome

Abstract

Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.

Keywords: disease associations; fecal transplant; human microbiome; microbial diversity; probiotics.

Figure 1

Major factors shaping the microbiome diversity. Illustrated are examples of multiple overlapping factors that shape the microbial composition including diet, stress, diseases, drugs, lifestyle, age, and host genetics. The outcome of these interacting factors are either healthy diverse, imbalanced, or dysbiotic microbiome which in turn affects the host health and diseases.

Figure 2

Microbiome and diseases association. Illustrated are examples of health and disease conditions that are linked to change in the microbiome. Health conditions associated with healthy microbiome include, as examples, protection from infections and radiation resistance. Diseases that result from imbalanced microbiomes are countless and include drug resistance, mental disorders, social diseases, obesity and metabolic syndrome, and sleep disorders.

Figure 3

Microbiome-secreted molecules and their effect on human health and diseases. The first panel of the Illustration shows some examples of well-defined secreted molecules that affects human health including (1) short-chain fatty acids (SCFAs) such as butyrate which play anti-inflammatory role and modulate the intestinal immunity and (2) lugdunin as an example to microbiome-based antibiotic produced by nose microbiome and target Staphyloccous. The second panel shows examples of microbiome-based metabolites that are associated with onset or development of diseases including: (1) trimethylamine N-oxide (TMAO)/cardiovascular diseases, (2) 4-ethylphenylsulphate/autism, and (3) colibactin/colorectal cancer.