Gut microbiota: next frontier in understanding human health and development of biotherapeutics

Abstract

The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required.

Keywords: biotherapeutics; dysbiosis; gut microbiota; human health; microencapsulation; probiotics.

Figure 1

Main beneficial functions of the human gut microbiota. Circles represent the three principal classes of functions performed by the bacteria that inhabit the gut. Arrows represent causal relationships. Abbreviation: SCFA, short chain fatty acid.

Figure 2

Proposed mechanisms whereby an altered microbial balance in the gut can lead to A) an increase in immune mediated disorders and B) chronic low-grade inflammation. Abbreviations: Th, T helper type; CD14, cluster of differentiation 14; LPS, lipopolysaccharide; TLR4, toll-like receptor 4.

Figure 3

Proposed mechanism whereby an altered microbial balance in the gut can A) be driven by foreign pathogenic invasion and further increase the likelihood of future infections, and B) lead to the promotion of carcinogenesis. Abbreviations: H₂S, hydrogen sulfide; ROI, reactive oxygen intermediate.

Figure 4

Proposedmechanisms by which an altered balance of the gut microbiota can lead to dysfunctional energy and lipid metabolism. Abbreviations: AMPK, AMP-activated protein kinase; ChREBP, carbohydrate regulatory element binding protein; FIAF, fasting-induced adipose factor; GPR41, G protein-coupled receptor 41; LPL, lipoprotein lipase; PYY, protein YY; SCFA, short-chain fatty acid; SREBP1, sterol regulatory element binding protein 1.

Figure 5

Computer-controlled dynamic human gastrointestinal (GI) model used for studies on the human gut microbiota. A) Schematic representation, B) photograph. vessels in series representing stomach, small intestine, ascending colon, transverse colon, and descending colon. All vessels can be continuously magnetically stirred; temperature can be controlled by the flow of hot water in the double jacketed vessel. Food can be given at a time interval and samples can be collected from any GI part at any time (eg, spent removal of the spent culture at defined intervals). This also allows for the administration of biotherapeutics, control of pH, enzyme, anerobic atmosphere and other GI parameters effecting gut microbiota.