+44 330 818 7254Ivana Haluskova Balter
Abstract:
Microbiome is a complex and diverse bacterial community specific to each individual crucial for human health. It is involved in immune mediated response and evolution of various diseases such us metabolic ones (diabetes,obesity), inflammatory diseases, (inflammatory bowel diseases), neurodegenerative diseases , psychiatric/behavioral disorders, respiratory diseases (allergy & asthma), cystic fibrosis (measurable changes in gut microbiome functionality occur in CF patients compared to controls), aging, response to cancer treatment, lipid metabolism. The gut healthy microbiome is able to convert lipids, including fatty acids or cholesterol, leading to the production of metabolites with potential health effects. Human microbiomes are a wide source of ARGs and a potential reservoir for pathogenic bacteria becoming more resistant. Various factors can modulate the human resistome, including the environment, diet, antibiotics, lifestyle and travel. This environment becomes a large source of ARGs for pathogenic bacteria, leading to the risk of infection due to multidrug resistant bacteria. Culture and metagenomics are two complementary methods developed to study these microbiomes in order to better understand the type of bacteria and ARGs present in the human body, as well as the factors that modulate the abundance and variety of these ARGs.
Keywords
Microbiome, Resistance genes, Antibiotic Resistance bacteria, Immune system, Drug resistance
Introduction:
Microbiome is composed from 100.000 miliards of bacterias and its weight is around 2 kg. It forms protective barrier against pathogens (permeability) and interactive layer with inner host immune system and neuroendocrine system. It does play important role in development (training of host immune response), human and reproductive health and need to be consider in diagnostic and prevention of diseases. The microbiota seems to have effects on the next generation from gestation, via maternal microbiota and immune responses. Various resistance genes found in the microbiome are highly similar to those providing potential resistance to chemotherapeutic agents in human pathogens, suggesting that the microbiome constitutes a good reservoir for antibiotic resistance.
The importance of human microbiomes is indisputable now as many new aspects of their roles have emerged in the past few years and continue to build a complex picture of metabolic interactions with their hosts. Similarly, animal and plant microbiomes studies have provided an exciting view into the potential benefits of healthy, diverse and stable microbiomes for sustainable agriculture. Understanding the persistence and spread of ARG in agricultural and other food production systems such as aquaculture will be critical for food safety and production. We are just beginning to reveal the importance of microbial assemblages in the environment for both bioremediation and biodegradation in addition to the vital roles played in nutrient cycles. Antimicrobial agents can have impact on all these activities in addition to spreading new gene combinations due to the rapid mobilization of ARGs due to the highly selective effects of antibiotic therapy. Whilst some antibiotics are natural products others are xenobiotics and remain and persist in the environment and mobile ARG will spread as a result of selection. Most naturally occurring resistance genes are chromosomal and further work is needed to investigate these impacts.
Observation :
Microbiome under 3 years old fluctuates substantially and is more sensible to environmental factors than the adult microbiome. Lifestyle, sanitation, caesarean sections, antibiotic usage, immunizations or responsiveness to vaccines interact with microbiome. It has been studied that there is a “critical window” early in life during which the microbiome can be disrupted in a way that may favour the development of disease later in life and there is and increasing evidence concerning role of microbiome changes during early life impacting the development of intestinal and extra- intestinal diseases. There are several pediatric diseases associated with alterations of the intestinal microbiome like Athopy and Asthma, Obesity and IBD (Crohn disease and Ulcerative colitis).
Antibiotic usage in early life can significantly impact the growth of otherwise dominant bacterial pyla in the human gut. Use of antibiotics can render infants susceptible to several diseases later in life according scientific evidence. Antimicrobials select for drug-resistant strains and their repeated use creates a host-specific reservoir of antimicrobial-resistance genes and organisms. Than as a risks linked with changed permeability and consequence of microbiome dysbalance might lead to invasion and subsequent diseases. (ex Clostridium difficile infections).
ARGs found in microbiota
The standard metagenomic studies and major culturomics studies dealing with ARGs have allowed identification of AR genes that are predominantly represented in the different microbiomes. These genes essentially involved antibiotics used in clinical practice and are carried by species which are minoritarian in the intestine.
Illustration :
As an ilustration of microbiome modulation or intervention for direct post-antibiotic effect which might develop - Clostridium diff. infections there is a support to research and development of antibodies, vaccine development and meantime use of microbiome modulation - FT- faecal tranplantation (with known limitations) in order to decrease also carriage of AR genes.
Targeted and individually specific intervention along with phagotherapy are other alternatives under exploration.The advantage of phage cocktails is that they generally will contain phages that infect more types of bacteria, so a cocktail can treat more strains or species and thus have broader applications. However better understanding and standardized approach evaluated in clinical trials still needed. thousands succumb to untreatable superbug infections on a daily basis.
Meantime 33,000 people die every year due to infections with antibiotic-resistant bacteria and real danger of post-antibiotic era exists. As noted previously , from long term perspective there is an impact on human health and increased risk for list of diseases noted above .Therefore microbiome (microbiome mediated response) from perspective of human health might be considered as a tool for diagnostic and prevention of several diseases as well.
Conclusion :
The relationship between gut microbes and the host immune system is predicted to be more unique in the gut than on other internal microbial environments. It is widely considered that commensal bacteria can induce a protective immune response to ensure host–microbial mutualism. Given all those facts and reality of raising resistance to TB drugs, antivirals, antiparasitic drugs, anticancer drugs, resistance is considered as one of the most significant challenges the world faces today.Host immune response empowering (microbiome/metabolome mediated immune response including data helping to diagnostic and accurate microbiome targeted interventions ), genetics and all alternatives to enhance immune response (vaccines, included those derived from microbiome) are possible alternatives to face it. Through these effects on the microbiome they may affect immune responses. Antibiotics need to be preserved and research supporting innovative research for new compounds protecting composition of microbiome and prevention of AR genes spread (veterinary medicine, environmental impact including) is important to consider and use accurate diagnostic to evaluate impact of adapted beneficial intervention on microbiome mediated immunne response. Further studies are warranted to identify both the putative ARGs present in the human microbiome, as well as the dynamics of their acquisition/exchange in the human microbiome.
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