Genomic Techniques Used to Investigate the Human Gut Microbiota

The human gut is the complex microbial ecosystem comprises more than 100 trillion microbes also known as microbiota. The gut microbiota does not only include about 400–500 types of bacterial strains, but it also contains archaea, bacteriophage, fungi, and protozoa species. In order to complete the characterization of the gut microbial community, we need the help of many culture-dependent and culture-independent genomic technologies. Recently, next-generation sequencing (NGS), mediated metagenomics that rely on 16S rRNA gene amplification, and whole-genome sequencing (WGS) have provided us deep knowledge related to important interactions such as host-microbiota and microbe-microbe interactions under various perturbation inside the gut. But, we still lack complete knowledge related to unique gene products encoded by gut meta-genome. Hence, it required the application of high-throughput “omics-based” methods to support metagenomics. Currently, a combination of high-throughput culturing and microfluidics assays is providing a new method to characterize non-amenable bacterial strains from the gut environment. The recent additions of artificial intelligence and deep learning to the area of microbiome studies have enhanced the capability of identification of thousand microbes simultaneously. Given above, it is necessary to apply new genome editing tools that can be used to design the personalized microflora which can be used to cure lifestyle-related diseases.

Intestinal Dysbiosis and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) affects 20–30% of the population, with an increased prevalence in industrialized regions. Some patients with NAFLD develop an inflammatory condition termed non-alcoholic steatohepatitis (NASH) that is characterized by hepatocellular injury, innate immune cell-mediated inflammation, and progressive liver fibrosis. In clinical practice, abdominal imaging, which reveals hepatic steatosis, is sufficient for NAFLD diagnosis if other diseases have been rejected. However, a liver biopsy is needed to differentiate NASH from simple steatosis. Therapeutic strategies used to treat obesity and metabolic syndrome improve NAFLD, but there is no specific treatment effective for NASH. The gut microbiota (GM) is composed of millions of microorganisms. Changes in the GM have a significant impact on host health. Intestinal dysbiosis is an imbalance in the GM that can induce increased permeability of the epithelial barrier, with migration of GM-derived mediators through portal vein to the liver. These mediators, such as lipopolysaccharides, short-chain fatty acids, bile acids (BAs), choline, and endogenous ethanol, seem to be involved in NAFLD pathogenesis. Given this evidence, it would be interesting to consider GM-derived mediator determination through omics techniques as a noninvasive diagnostic tool for NASH and to focus research on microbiota modulation as a possible treatment for NASH.

Contribution of Gut Microbiome to Human Health and the Metabolism or Toxicity of Drugs and Natural Products

Trillions of microorganisms with a complex and diverse community are in the human gastrointestinal tract. Gut microbial genomes have much more genes than human genome, thus having a variety of enzymes for many metabolic activities; therefore, gut microbiota is recognized as an “organ” that has essential functions to human health. There are interactions between host and gut microbiome, and there are correlations between gut microbiome in the healthy state and in certain disease states, such as cancer, liver diseases, diabetes, and obesity. Gut microbiota can produce metabolites from nutrients of dietary sources and from drug metabolisms; these metabolites, for example, short-chain fatty acids (SCFAs), have substantial effects on human health. Drug-microbiome interactions play a crucial role in therapeutic efficiency. Some drugs are able to change compositions of gut microbiota, which can lead to either enhance or reduce therapeutic efficiency. This chapter provides an overview of roles of gut microbiota in human health and diseases and recent research studies on the metabolism or toxicity of drugs and natural products. Since gut bacteria considerably contribute to drug metabolism, research on the influence of gut microbiome on drug candidates (or natural products) should be part of the drug development processes.

“Dialogue” between the Human Microbiome and the Brain

In conditions of severe gut dysbiosis, there is a risk of developing diseases of the host organism in general and of the brain in particular, as evidenced by a growing number of studies. This chapter focuses on several groups of low-molecular-weight compounds that originate primarily from the gut microbiota. It discusses the results of experimental and clinical studies on the effect of microbial metabolites (such as short-chain fatty acids, phenolic metabolites of tyrosine, indolic metabolites of tryptophan, trimethylamines) on the brain. Several studies have proven that the microbial metabolite profiles in the gut and serum are interlinked and reflect a disruption of the gut microbial community. Using 16S ribosomal RNA gene sequencing, it was found that the gut microbiota of patients with positive or negative dynamics of neurological status differ taxonomically. The chapter also presents data obtained from animal germ-free (GF) models. Many researchers would like to consider the gut microbiota as a new therapeutic target, including for the treatment of brain diseases, stroke prevention, reduction of neuroinflammation, and more successful neurorehabilitation of patients.