Tuesday 27-02-2024 - 16:00

Exploring the Human Microbiota: Insights, Challenges, and Novel Discoveries

Elisa Pierella, DTA3 Alumna, University of Central Lancashire

Humans are superorganisms

Our understanding of the human body has evolved. We used to think it was solely composed of our own cells, but now we recognize ourselves as 'superorganisms.' This means we're not alone – our bodies harbor microbial organisms, mainly bacteria, collectively known as the microbiota. These bacteria vary across different body areas such as the mouth, nose, skin, and vagina, with the highest concentration observed in the gastrointestinal (GI) tract¹. The colon, the final portion of the GI tract, reaches its microbiota peak with an estimated 10¹⁴ microorganisms and nearly 2,000 different bacterial species. Each of these bugs contains its own genetic material, forming a collection of genes that surpasses the number found in the human genome by over 100 times. The gut's microbiome, a compilation of their genes, is even more impressive – containing over 100 times the genes found in each individual human genome²!

The gut microbiota plays an expansive and pivotal role in maintaining overall health. Its multifaceted functions include not only defending against pathogens but also actively participating in the generation, metabolism, and absorption of essential nutrients. Moreover, the gut microbiota contributes significantly to the development of a robust immune system and performs various other indispensable roles within the body^1,3. Notably, emerging research has connected the gut microbiota to a range of health conditions beyond its traditional roles, including heart diseases, respiratory diseases, mental health issues, and more. Interestingly, some bacterial species within the gut microbiota demonstrate a dual nature, serving both as beneficial allies and potential adversaries to the integrity and function of the gut. This duality highlights the intricate balance and dynamic interplay between the gut microbiota and the host, underlining the complexity of their relationship and its profound implications for our well-being.

Infectious agents – out microbiome can be a reservoir

Infectious diseases stand as a significant global cause of mortality, ranking among the top four causes of death in high-income countries in 2019, particularly with respiratory and bloodstream infections proving to be the most fatal⁴. The year 2019 witnessed 13.7 million deaths globally attributed to infections, with 3 million occurring in children⁵. In the United Kingdom, infectious diseases were estimated to contribute to 10% of all deaths, accounting for 7% of potential life years lost and 8% of hospital bed days, incurring an annual cost of up to £30 billion in the country⁶. The impact of infectious diseases extends beyond mortality, encompassing long-term consequences such as increased morbidity, prolonged hospital stays, escalating healthcare costs, and the looming threat of antimicrobial resistance (AMR). Vaccinations, antimicrobial drugs, and enhanced hygiene practices present an opportunity for non-communicable diseases to surpass infectious diseases as the primary cause of death globally⁷.

The World Health Organization (WHO) recently identified antibiotic-resistant “priority pathogens”, categorizing them based on their level of antibiotic resistance in 2017. Notably, some of them are members of the gut microbiota, therefore indicating that the gut is also a reservoir of microbes leading serious infections⁸.

Despite political prioritization and guidelines for antimicrobial stewardship and infection prevention and control, resistance levels persist at concerning levels. Besides known measures such as reducing the misuse of antibiotics, emerging strategies have been suggested, for instance, considering the modulation of the human microbiota as a pioneering approach to outcompete potential pathogens and combat the threat of AMR.

Decoding the complexities of the gut microbiota

Investigating the intricate bacterial communities residing in the gut and examining their unique genetic composition for each individual pose a captivating yet challenging task. Innovative and recent approaches aim to replicate the gut ecosystem in vitro, enabling a controlled assessment of physiological oxygen gradients, cutting-edge methodologies which are valuable to deepen our understanding of the mechanistic aspects of the gut microbiota⁹.

Although the literature offers extensive insights into how microbial communities vary in response to lifestyle changes, behavioural shifts and illnesses, the understanding of cellular and molecular processes driving microbiota shifts and adaptation, along with their consequential impacts on the host environment, remains largely unclear. Fundamental queries such as the definition of a healthy gut microbiota, what factors trigger the transition from physiological to pathogenic gene expression, what parameters limit the establishment of incoming healthy bacteria or facilitate the colonization of disease-causing bacteria, are still unrevealed.

What's next

Given the previously highlighted knowledge gaps, it is imperative to delve deeper into understanding the dynamics of diverse bacterial polupations typically inhabiting the human gut. This entails:

• elucidating how these species coexist, distribute the space and compete with each other and with the host cells
• unveiling potential correlations between bacterial phenotypes and genome-wide alterations in genes associated with both physiological functions and virulence factors

The integration of diverse methodologies is key to kickstarting this exploration, from humble and conventional microbiological techniques to advanced analytical methods to scrutinise molecules such as genes, transcripts, and proteins. The multifaceted approach holds promise for initiating innovative inquiries about the intricate and complex world of  the human microbiome.