The microbiota, chemical symbiosis, and human disease

Abstract

Our understanding of mammalian-microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, as well as unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments-nasal, lung, and gastrointestinal tract-is reviewed with a focus on new knowledge about the taxa, species, proteins, and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota: Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa, as well as cystic fibrosis, chronic obstructive pulmonary disorder, and asthma in the pulmonary tissues. For the vast and microbially dynamic gastrointestinal compartment, several disorders are considered, including obesity, atherosclerosis, Crohn's disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow and suggests new opportunities for modulating this symbiosis using designed interventions.

Keywords: epithelia; intestine; lung; mucosa; nasal sinuses.

Figure 1

The small 18 cm² surface area of the Nasal-Sinus Compartment is skin-like at the nostrils but is then lined by mucosal epithelia (mucosa) and colonized with microbiota (orange). Air, including particulate and some biological matter, is passed through on its way to the lungs, the major output, although some mucus-entrapped matter is passed to the gastrointestinal tract. Small arrows across the mucosa indicate local absorption and secretion, including mucus delivery. Chemicals absorbed across this still external nasal-sinus mucosa then enter the human body, passing through the plasma and into the heart for circulation. Diseases associated with the nasal-sinus compartment represented are Staphylococcus aureus infection and rhinosinusitis, with some features highlighted (see text for details).

Figure 2

The larger 70-100 m² surface area of the Lung Compartment is composed of the UPPER more microbial colonized airways and the LOWER airways that are non-sterile but contain microbiota (orange). Local exchange of materials across the mucosal epithelia that line this compartment (mucosa) are indicated by the small arrows, and materials absorbed into the human body via this route, including O₂, are carried by the plasma to the heart for circulation. Microbiota features of the lung diseases cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD), and asthma associated are highlighted, and are elaborated in the text.

Figure 3

The vast 250 m² surface area of the Intestinal Compartment is colonized by a diverse community of trillions of commensal bacterial cells (orange) and lined by mucosal epithelia (mucosa) unique in structure and function to each region of the GI tract. Local exchange across the mucosa are indicated by small arrows. Distinct from the other major mucosal tissues presented here, materials absorbed from the intestinal compartment pass via the portal vein to the liver (red) prior to potentially reaching systemic circulation. Furthermore, this compartment is also distinct in having two major input sources, the food and other materials from the oral cavity, and the liver-generated bile (blue) and other secretions from the local organs like the pancreas and gall bladder. Features associated with the microbiota and diet and obesity, cardiovascular disease (CVD), inflammation, and drug toxicity are highlighted. Some links to the unique roles the bile and liver play in sending and receiving, respectively, material from the GI are noted. As indicated, the GI microbiota also impact the other compartments considered via the immune system.