The microbiome: a perfect relationship

The microbiome is a current “trendy hot topic” in medicine, causing cross-specialty excitement from psychiatry to oncology. But what exactly is the microbiome? And why has it attracted so much interest from the medical and scientific community?

The human microbiota is the community of microorganisms that resides in the human body and primarily consists of the “gut flora”, the niche of bacteria living in the human intestine among others.

The microbiome, referring to the genes harboured by the bacterial cells, meanwhile, is used to describe the bacteria collectively. The microbiome is now considered to be an important part of the human genome.

Infants first acquire their microbiome during vaginal delivery from their mother, including microbes that aid digestion of the mother’s milk. Those born by Caesarean section have vastly different microbiomes to those born vaginally, and these differences are now thought to impact upon health.

The microbiome develops continually over the first 3 years of life, by which time it stabilises and resembles that of adults. What we eat rapidly affects the composition of the microbiome; within a few days of a significant diet change, not only are there alterations in species diversity, but also in the genes the bacteria express.

This is thought to have had evolutionary advantage during seasonal changes in food availability, allowing for maximum nutrient absorption. Additionally, the medicines we take and hygiene practices within the scope of modern public health have all impacted on the composition of our microbiome, coinciding with recent increases in allergic, inflammatory and auto-immune diseases.

Indeed, the human microbiome has been implicated in a plethora of diseases, ranging from diabetes, obesity, inflammatory  bowel diseases, cancers, and even depression and (potentially) autistic spectrum disorders.

Obesity is the epidemic of the 21st century. The species composition of the gut microbiome has been found to differ between the obese and the lean in both mice and humans, with evidence that the obese microbiome contributes to weight gain by yielding more energy from diet.

It is now well established that obesity-associated chronic inflammation is implicated in the development of type 2 diabetes. This opens up possibilities of new therapies to treat, and perhaps prevent diabetes by modifying the microbiome.

Apart from diabetes and the metabolic syndrome, which are now understood to be in part chronic inflammatory diseases, the intestinal microbiome has also been implicated in autoimmune diseases affecting the bowel, such as inflammatory bowel diseases (IBD).

The microbiomes of IBD patients have been shown to fluctuate more than that of a healthy person and overall species diversity is reduced in these patients. This has led to the potential of using the microbiome as a diagnostic tool, and of course of altering the microbiome as a therapeutic option.

The microbiome in IBD has been one of the most studied in terms of both disease pathogenesis and treatment. It has been postulated that the mucosa within the gut develops a pathogenic immune response toward the microbiome and it is this that drives inflammation .

There are also a number of researchers showing interest in the role of faecal transplant in IBD, with studies showing safety, albeit with variable efficacy. Studies have also demonstrated increases in anti-inflammatory cytokines when giving IBD patients probiotics.

The microbiome has been implicated in other bowel diseases, from irritable bowel syndrome (IBS), where alterations in the microbiome may play a role in small bowel inflammation, to colorectal cancers, where once again the microbiome has been noted to be significantly different to that of the healthy population.

Inflammation associated with the microbiome can both cause and contribute to tumour progression. This has led to studies demonstrating a link between diet and cancers, with diets high in fibre and low in fat changing the mucosal biomarkers of cancer risk. Moreover, bacteria may have anti-tumour properties as animal studies have demonstrated that probiotic use in early colorectal lesions can halt progression.

Another aspect that has caused excitement in scientific and medical circles is the emerging link between the gut and the brain. This is becoming increasingly acknowledged, both in gastroenterology and psychiatry, placing cross-specialty symbiosis at the forefront of doctors’ minds. The gut-brain axis is established before birth and continues throughout life, operating primarily through the vagus nerve.

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The link between the microbiome and depression has been extensively studied in animals. Rats fed with certain bacteria have been shown to develop signs of depression and anxiety which are improved by giving beneficial bacteria.

New evidence is also emerging that suggests just how deeply connected humans are to their gut microbiome; faecal transplant recipients have been shown to take on both the physical and the personality traits of their donor, including obesity, underweight and in some cases, even mental illness such as depression.

 

So, what does this mean for medicine and public health?

Worldwide movements towards the so-called “western diet” contributes to adverse alterations of the human microbiome. As knowledge of the importance of the microbiome grows, so does the importance of diets compatible with a healthy gut flora; prebiotic diets that promote growth of beneficial bacteria.

Similar to the concept of symbiosis with helminths, it is possible that the old public health, which focussed on communicable diseases, hygiene and antibiotics, has indirectly led to concepts in new public health; chronic, non-communicable “lifestyle” diseases.

The idea that we are simply “too clean” is one that is gaining much momentum. This excessive hygiene and over-use of antibiotics has altered our microbiome and eradicated potentially helpful organisms with which we have evolved a symbiosis.

It is postulated that the important symbiotic relationships humans developed over thousands of years with the microorganisms that reside within them hold the key to human health.

Whilst hygiene remains important, particularly in the context of antibiotic resistance and emerging “super-bugs”, perhaps some balance is required if we are to conquer the emerging epidemic of inflammatory diseases. The microbiome could provide a novel way of doing just that.