Our Microbiome Magic

What is the Microbiome?

The human body is home to a huge and diverse community of microorganisms, consisting of bacteria, fungi, protozoa and viruses. Collectively these organisms are referred to as the microbiota, and the collection of genomes from these microorganisms is referred to as the microbiome, however the two terms are often used interchangeably. 

It is estimated that over 10,000 species of microorganisms occupy the human microbiota, and that there may be more than eight million unique genes associated with the various microbiomes in the human body. The number of microorganisms present in the human microbiota is thought to be slightly higher than that of human cells in the body, and some have classified the microbiome as an organ in its own right. 

Microorganisms inhabit many parts of the human body, including the gastrointestinal tract, skin, saliva, oral mucosa and conjunctiva, with the vast majority residing in the colon. Each of these microbiomes is distinct depending on the location in the body, and the relationship is generally mutually beneficial.

The microbiome plays a critical role in human health, supporting processes such as:

• Maintaining intestinal integrity and supporting barrier function
• Breaking down food
• Providing essential nutrients and beneficial short chain fatty acids such as butyrate
• Regulating the immune system, for example modulation of lymphoid structure development and T cell differentiation
• Protecting against infection through secretion of bacteriocins and antagonizing pathogens
• Contributing to mental health
• Regulating metabolism

There have been significant advances in our understanding of the human microbiome in recent years as advances in genome sequencing technologies and metagenomic analysis have enabled scientists to study these microbial communities. Tremendous variation can be observed in terms of the species that make up a person’s microbiome, and even within an individual these microbial communities can shift depending on factors such as diet, medication, age, stress levels and other environmental factors. The microbiome has become a hot topic for research recently, as when the balance of the microbiota is disturbed the microbiome can contribute to a range of diseases and conditions including cancer, diabetes, inflammatory bowel disease, autism, anxiety and obesity.

Microbiome research is changing our perception of human biology and it is now becoming apparent that we must consider the microbes with which we have coevolved as a critical factor in health and disease.

The Gut Microbiome and Gut-Brain Axis

To date a major focus of human microbiome research has been studying the bacteria in the gut. The gut microbiota represents the largest and most diverse community in the human microbiome. The gut microbiota is dominated by strictly anaerobic organisms, with members of the Firmicutes and Bacteroidetes phyla as the most dominant species followed by Proteobacteria and Actinobacteria. 

The adult gut microbiota is resilient against minor perturbations, however more significant influences such as antibiotic treatment or disease onset can lead to dramatic changes in the microbial community composition. An individual’s genetics, diet and environment also play a major role in shaping the gut microbiota.

The gut microbiome plays an important role in metabolism and regulating the immune response, but its impact can also be observed on the brain, where microbial metabolites influence mood and behavior via pathways that connect the gut to the central nervous system, including direct activation of the Vagus nerve from the enteric nervous system, production of metabolites that pass through the intestinal barrier into the circulatory system, and modulation of the immune system through metabolites and microbial associated molecular patterns.

There is increasing recognition that psychiatric and neurological illnesses frequently co-occur with gastrointestinal pathology, and studies indicate that the composition of the host microbiome affects neurological function and leads to effects including depression and anxiety, and treatment with certain species of Lactobacillus or Bifidobacterium probiotics can reduce anxious and depressive behavior.

As we begin to understand how the microbiome influences the brain and behavior this opens up possibilities for rationally designed therapeutics to treat mental health illnesses that are currently treated by pharmacological alteration of neurotransmitters, for example selective serotonin reuptake inhibitors that are commonly used to treat depression.

Microbiome Therapeutics

Therapeutic manipulation of the microbiome is a rapidly advancing field and data suggests that treatments capable of reversing a damaged, dysbiotic microbiome are effective in managing certain human diseases. 

There is also potential in the future to use the microbiome as a drug delivery system, for example through the use of engineered probiotics containing genetic circuits to enable production of therapeutic proteins upon detection of disease biomarkers, enabling on-demand drug release.

As we move forward with efforts to manipulate the microbiome to enhance health and therapeutic responses there is still a lot to learn around the mechanisms by which the microbiome exerts its effect. Understanding the factors that govern the composition of the gut microbiota will be of critical importance in designing successful microbiome therapeutics, and developing microbiome therapies that are robust enough to withstand the diversity and an individual’s microbiome will be a major challenge. 

One of the biggest challenges in microbiome research is determining whether a change in the microbiota is responsible for a specific condition, or if it is a side effect of having the condition. The complex nature of the microbiome and the fact that every person has a distinct one makes it challenging to determine cause-effect relationships.

What Could the Future Hold?

Microbiome research looks set to continue as a high growth area, as demonstrated by an increase in the number of published articles on the topic of cancer-microbiome interactions of nearly 2000% between 2005 and 2015. There is still much research to be done to understand the functional links between the microbiome and disease, but this work is opening up a vast range of opportunities in human health.

Future opportunities in microbiome research could potentially include areas such as:

• Accurate control over manipulation of microbiome, e.g. through the use of phage therapy.
• The microbiome as an integral part of precision medicine, with fingerprinting of a patient’s microbiome becoming a complementary tool to determine how likely a patient will be to respond to treatment.
• Enhancement of existing therapies by co-administration of rationally designed, patient specific, precision probiotics.
• The microbiome as a drug delivery system, for example engineered probiotics containing genetic circuits to enable production of therapeutic proteins upon detection of disease biomarkers enabling on-demand drug release.
• An expanded library of prebiotics to stimulate a diverse range of beneficial bacteria.