How the Gut Microbiome Influences Human Health

The gut microbiota: A complex world of microorganisms

The human body is a bustling metropolis of microorganisms, from bacteria to viruses to fungi, all working together to form the mysterious and complex world of the human microbiome. These microbes live in various parts of the body, including the skin, mouth, gut, and reproductive system. In fact, the number of microbial cells in our bodies is estimated to be roughly equal to our own human cells [1], with the majority of these microorganisms inhabiting the gut.

The gut microbiome plays a vital role in regulating several aspects of human health and behavior from digestion to the immune response, and even our mood. In addition, changes in the gut microbiota composition and function have been linked to a wide range of chronic diseases, including gastrointestinal inflammatory and metabolic conditions, as well as neurological, cardiovascular, and respiratory illnesses.

Using next generation sequencing techniques such as 16S rRNA gene sequencing and metagenomic sequencing, researchers have revolutionized our ability to study the human microbiota by enabling the identification and quantification of microbial species and their functional products. These methods have revealed the immense diversity of the human gut microbiota, as well as the unique microbial signatures that are associated with various human disorders.

Associations between the gut microbiota and a wide range of chronic disorders highlight the importance of understanding the microbiome and its role in health and disease. This blog discusses how advances in techniques like metagenomics can reveal the vast diversity of the microbiome and it’s potential for new diagnostic and therapeutic applications.

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The link between the gut microbiota and chronic diseases

Advances in high-throughput sequencing techniques have allowed for the profiling of the human microbiota in unprecedented detail. Traditional microbiology techniques relied on growing bacterial species in a lab environment, however, environmental microbiologists estimate that less than 2% of bacteria can be cultured in the laboratory [2]. Therefore, it is only with the advent of sequencing technologies that we now have the ability to study complex microbial communities in their entirety, without the biases of culture.

Metagenomics presents a particularly powerful tool that can directly sequence and analyze DNA from the entire microbial community in a given sample. Researchers can use this approach to not only reveal the identity of species present but also provide insight into the metabolic activities and functional roles of those microbes.

For example, metagenomic studies of the human gut microbiome have revealed the presence of genes involved in the production of short-chain fatty acids (SCFAs), including butyrate, propionate, and acetate. SCFAs are made from fermentation of dietary fiber and resistant starch, and are associated with particular bacterial species in the gut [3]. For example, the production of propionate and acetate is associated with the abundance of Bacteroides spp., while butyrate is produced mainly by the Firmicutes phylum [4,5]. SCFAs have been shown to regulate numerous metabolic pathways in various organs, including the gut, liver, adipose tissue, muscles, and brain [6].

Strikingly, numerous studies refer to the fact that many chronic illnesses, including type 2 diabetes [7], heart disease [8,9], asthma, [10], and inflammatory diseases [11-13] are also associated with a decreased abundance of bacteria that produce SCFAs, particularly butyrate.

Butyrate is a particularly important SCFA because it is a key energy source for epithelial cells in the colon, has been linked to anti-inflammatory effects, and has been shown to impact various genetic pathways including the cell cycle, cell differentiation, and fatty acid metabolism [14].

By identifying the effects of particular SCFAs and the bacteria responsible for their production, researchers can better understand the factors that prevent or lead to disease and start incorporating this knowledge into therapeutic treatments.

The power of metagenomics analysis

Metagenomics can provide information on the functional potential of the entire microbiota community, the genetic diversity of the bacterial species present, and key differences between healthy and unhealthy microbiota. The association between disease susceptibility and microbiota compositions can be used to identify potential biomarkers and novel therapeutic targets, and develop targeted therapies that can modulate specific microbiome functions via diet, genetic editing, and other procedures like fecal microbiota transplantation (FMT).

These microbiome-based therapies are still in their infancy but are already showing great promise. For example, a randomized controlled trial demonstrated that FMT was highly effective in treating recurrent Clostridioides difficile infection, with a success rate of over 90% [15]. Additionally, several studies have now found that the direct administration of SCFAs like butyrate can induce beneficial effects, including improved insulin sensitivity and increased energy expenditure in mice [16,17], leading to potential new therapies for type 2 diabetes.

There is also emerging evidence that the gut microbiota can influence the efficacy of cancer immunotherapy, suggesting that microbiome-based therapies may have potential applications in oncology [18,19].

While more research is needed, the early results suggest that microbiome-based therapies have the potential to revolutionize the way we approach the treatment of various health conditions.

Future perspectives

The field of microbiome research has been transformed by techniques such as targeted sequencing, metatranscriptomics, and metagenomics analysis. These approaches have allowed researchers to explore the complex interactions between the microbiota and the human body, uncovering specific bacterial species and their functional potential. This improved understanding of the microbiome’s role in human health and disease has paved the way for new therapeutic interventions.

Early attempts to rehabilitate perturbed gut microbiota via dietary intervention, microbial supplementation, or FMT has already resulted in positive results, demonstrating the potential of the gut microbiota as a therapeutic target. However, it is important to note that microbiome-based therapies are still in their early stages and there is a lot we do not yet understand. For example, it is unclear how changes in the microbiome interact with other factors such as genetics, lifestyle, and environmental exposures, and how these interactions affect overall health outcomes.

The use of techniques like targeted sequencing, metatranscriptomics, and metagenomics analysis has opened up new avenues for understanding the interactions between the entire microbiota community and the human body. With continued research, effective therapeutic treatments could be developed for everyday use, leading to better overall health and disease prevention.

At Eremid, our world-class research teams have experience in extracting, analyzing, and interpreting sequencing data from microbiome samples, supported by the latest genomics technologies.

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 References

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