Listen to your gut

Drawing of the gastrointestinal system with microbes surrounding it to illustrate the gut microbiome

Artwork by Daniel Coneyworth

This article was originally published in The Oxford Scientist Hilary Term 2022 edition, Regeneration.

Dating back to Hippocrates’ teachings on the benefits of fibre-rich diets in 430 BC, eating habits have traditionally been connected to health. What have we learned since then about diets, our gut, and its microbial inhabitants?

In the 19th century, German paediatrician Theodor Escherich consolidated the study of the human gut microbiome; today the bacterium Escherichia coli is named after him. Henry Tissier studied the administration of beneficial bacteria in the human gut and Ilya Metchnikov investigated the merits of lactic acid bacteria in fermented milk for a healthy life. Alfred Nissle isolated a bacterial strain E. coli Nissle 1917, which he found to be antagonising the growth of harmful bacteria.

Since 2012, scientists have been investigating the gut in the Human Microbiome Project: our gastrointestinal (GI) tract harbours approximately 100 trillion microorganisms, a number exceeding that of human cells by tenfold. Our gut microbiome—a complex and dynamic population—consists of bacteria, yeast, fungi, archaea, and viruses. We live in symbiosis with these microbiota, and a balance of “good” and “bad” organisms is crucial for our health.

The first weeks of life are of paramount importance in the formation of the microbiome. After birth the GI tract is rapidly colonised although, interestingly, microorganisms can already be found in the placenta pre-birth.

Whether or not the vaginal flora influences the newborn’s microbiome during birth is currently being debated, however, it is known that newborns delivered by Caesarean section possess a less diverse microbiome. This is typically associated with the sterile hospital environment, and by nine-months of age the differences in the microbiome are negligible.

The earliest microbiome populations are comprised of Bifidobacteria which are specialized in the digestion of human milk sugars, a fact which highlights the symbiotic co-existence of bacteria and their human host. By around age two and a half the human microbiome resembles that of an adult in terms of its composition and function, especially during processes such as food degradation, vitamin synthesis, lipid metabolism, maintenance of the intestinal barrier, and the suppression of harmful microbiota.

Throughout our life, there are factors such as diet, illness, or antibiotic treatment that continually disturb the dynamic population of our gut.

In adults, the ratio of Bacteroidetes (responsible for polysaccharide metabolism) to Firmicutes (involved in lipid metabolism) can be utilised as an indicator of microbiome and host health. Over 75% of the microbiome is formed by a stable core population of microbiota, an imbalance of which, called Dysbiosis, can harm the intestinal barrier and enhance inflammatory processes.

Detrimental imbalances are thought to contribute to ageing as well as diabetes, cancers, and the pathogenesis of cardiovascular and neurodegenerative diseases. A significant decrease in microbial diversity has been found in aged individuals, a state which offers harmful species the opportunity to prevail. These changes are not only connected to mobility, diet, previous illness, and medication, but also to the individual’s genetics and geological location.

The intestinal barrier is vital to the co-existence of host and microbiome as it separates the two whilst maintaining an immune acceptance state. Immune receptors in our gut detect microbial motifs and can, if needed, adjust the production of antimicrobial substances, and induce inflammation. Recurring inflammations are harmful to our organism and lead to deterioration of the gut lining. By consequence, the leakage of microbes and their excretions into the blood stream can result in activation of the systemic immune system.

With our ageing population an understanding of Alzheimer’s disease is becoming more and more necessary. Researchers have examined the link between inflammation caused by microbiota and the formation of amyloid plaque in the brain which is responsible for the development of dementia. They found that the gut microbiome influences the immune system and its effect on the nervous system via bacterial excretions. Certain microbial markers, such as Lipopolysaccharides which are anchored on bacterial membranes, were associated with amyloid plaque quantity in brain tissue. Current work focusses on identifying bacteria involved which could open up the possibility of preventative strategies.

Antibiotics are indispensable life savers and facilitate recovery from common infections. Nevertheless, most antibiotics are so-called ‘broad-spectrum’ antibiotics which work more like a sledgehammer than a precision tool and tend to harm our whole gut microbiome.

Clostridium difficile is a bacterium populating the healthy human GI tract: under prolonged antibiotic treatment, this harmful species can gain the upper hand and excrete noxious toxins which later damage the intestinal barrier and cause diarrhoea or more serious complications such as sepsis.

It was assumed that the healthy gut microbiome can fully recover from an antibiotic, but under prolonged drug treatment the initial microbiome composition might not be re-established. Pre-biotics (fibres that cannot be digested by the host but serve as nutrients for bacteria in the lower GI tract) and pro-biotics (formulations containing presumably beneficial bacteria for a healthy gut microbiome) are being investigated as preventive or supportive measures.

A healthy gut microbiome—what is that? In 2012, the International Life Sciences Institute North American Microbiome Committee commissioned academic, government, and industry experts to review this question. They concluded that a healthy microbiome population cannot be easily defined, but on the whole is more resilient toward perturbations. The distribution of certain microbial species may elevate the risk of infections and diseases, although it is yet unknown whether dysbiosis is a cause or a consequence of illness. Overall, high diversity in the microbiome is associated with health, and poor diversity with disease.

Our lifestyle and diet directly influence the gut microbiome and its metabolic end-products. Diets with high salt and refined carbohydrate consumption, coupled with low fibre intake, are presumed to lead to a decrease in microbial diversity.

Food type, and quality, appear to be important for a healthy microbiome as well as physical exercise. Foods that are especially rich in fibres include fruits, vegetables, and grains. Despite the recommendation of around 30g of fibre for an adult per day, the average Western diet contains around 20g daily. If the fibre content of a banana is around 2g / 100g, with an average weight of 118g per banana one would need to eat around 13 bananas to reach 30g of fibre—and drink plenty of water for sufficient hydration.

Fluctuations in our microbiome due to diet can be reverted. For pre-biotics, no causal connection to microbiome and host health can be made at this point, as fibre may be effective independently from an individual’s microbiome composition. For pro-biotics, mostly temporal persistence of the pro-biotic formulation in the GI tract has been shown. The prevalent microbiome is known to be “colonisation resistant” against incoming, unfamiliar microbiota. Nonetheless, administered pro-biotics could influence the commensal bacterial species indirectly by modulating the transcriptional activity in these species.

All in all, we only know little about our gut microbiome, and we are just beginning to understand the complex coherence between microbiome and host health. Elaborate studies are aiming to define a healthy microbiome and its biomarkers whilst examinations of fibre, pre- and pro-biotics are trying to elucidate the mechanistic link between microbiome and host. Furthermore, modern studies aim to understand the GI tract as a whole by investigating the mutual influence of genes, proteins, and metabolites of gut bacteria. The microbiome remains a fascinating field of research and all evidence points toward the need to listen to our gut.