What is the gut microbiome and what does it do?
The gut microbiome is a diverse micro-ecosystem that is home to trillions of micro-organisms, including bacterial microbes, viruses, fungi and protozoa. The dominant species of the gut microbiota include Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia. The two predominant bacterial groups occupying the gut microbiome are gram positive Firmicutes and gram negative Bacteroidetes which represent 90% of the microbiota of the gut. Lactobacillus, Bacillus, Clostridium, Enterococcus and Ruminococcus belong to the Firmicutes phylum. Bacteroides and Prevotella are the predominant genera of Bacteroidetes.
In healthy individuals, the gut microbiota differs in various areas of the gastrointestinal tract (GIT) and will change over time, being influenced by age and environmental factors including dietary habits, antibiotic consumption and lifestyle choices. Differences in the composition of the microbiome have also been observed between different ethnic groups.
The ratio of Firmicutes/Bacteroidetes (F/B) bacteria play an important role in intestinal homeostasis. If the ratio of F/B are out of balance, dysbiosis can occur. An increased ratio is observed in those with obesity and a decreased ratio can be seen in people with inflammatory bowel disease (IBD). It is important to note that there is no singular optimal gut microbiota composition, however a rich and diverse microbial community leads to a thriving, well-balanced and healthy gut microbiota.
The microbes of the gut have a key influence on many aspects of our health, including protecting against pathogens and the regulation of endocrine, immune and metabolic function. They can also influence drug absorption and metabolism.
Functions of the microbiota
The gut microbiota in humans has three main functions: metabolic, defensive and trophic.
- The metabolic function of the gut microbiota occurs after the consumption of food to recover energy and nutrients and is also involved in a fermentation process for non-digestible complex carbohydrates (cereals, vegetables, fruit, fructo-oligosaccharides and processed foods). This process produces short-chain fatty acids (SCFA) which are thought to play a key role in the gut-brain relationship.
- The defensive function helps to prevent invasion and overgrowth by competing with fungi (e.g. Candida) or bacteria (e.g. Clostridioides difficile) for attachment sites and nutrients.
- The trophic function is involved in the regulation of the immune system and the central nervous system by promoting epithelial cell proliferation and differentiation and the stimulation of the intestinal motor and neuro-endocrine pathways found in the gut.
Comparisons of different diets and their effect on the gut microbiota
Several studies of gut microbiota composition in vegans and vegetarians have shown higher ratios of Bacteroides/Prevotella, Bacteroides thetaiotaomicron, Clostridium clostridioforme, Klebsiella pneumoniae and Faecalibacterium prausnitzii when compared to omnivores. The increased consumption of polyphenols in vegan and vegetarian diets have also been shown to increase the abundance of Bifidobacterium and Lactobacillus, however further studies are required to confirm the precise influence that plant-based diets have on the gut microbiome.
Gluten free diets that are followed by individuals with coeliac disease, wheat allergy or a gluten intolerance/sensitivity have shown to result in a decrease of Bifidobacterium and Lactobacillus (the ‘healthy bacteria’), and an increase in detrimental species like Enterococcus, Staphylococcus, Salmonella, Shigella and Klebsiella. This can potentially influence the profile of the microbiome and affect long-term homeostasis of the intestinal mucosa. Nevertheless, it is essential that those affected by coeliac disease strictly adhere to a gluten-free diet to avoid adverse health outcomes.
Ketogenic diets consist of very high-fat and very-low carbohydrate intake and are sometimes used to help treat individuals with drug-resistant epilepsy or GLUT1 Deficiency syndrome. Studies on the gut microbiota in patients following a ketogenic diet have shown that decreased polysaccharide intake (due to low carbohydrate consumption) can result in a decrease in Bifidobacteria and an increase in Akkermansia or E. coli, which may cause detrimental effects on the gut mucus barrier.
Low FODMAP Diets have been used to help treat symptoms of IBS and IBD. FODMAP describes a group of poorly absorbed but highly fermentable carbohydrates and polyols. One study taken of patients with IBS on a low FODMAP diet found a total reduction in bacterial abundance of 47% when compared with a habitual diet. When a low FODMAP diet was consumed in conjunction with supplementation with probiotics, Bifidobacterium levels appeared to be restored to healthier levels and imbalances in the gut microbiota were counteracted.
The typical Western Diet, that is high in additives, saturated fats and sugar has been shown to cause alterations in the function of the intestinal barrier and permeability. This can lead to changes in the activation of immune cells and reduced microbial diversity leading to dysbiosis and potentially higher incidences of metabolic conditions and obesity. Evidence suggests that diets higher in glucose or fructose can increase the ratio of Firmicutes/Bacteroidetes and the proportion of Proteobacteria (a large source of Lipopolysaccharides) which may alter gut permeability and increase systemic inflammation.
The Mediterranean Diet which is associated with increased consumption of mono-unsaturated and poly-unsaturated fatty acids, polyphenols, antioxidants, prebiotic fibres and a higher incidence of plant-based proteins is associated with an increased abundance of healthier levels of Bacteroides, Bifidobacterium and higher total SCFAs. The Mediterranean Diet continues to remain the most beneficial solution to improving diversity and stability of the microbes, ensuring regular permeability and healthy immune function.
Carbohydrate intake – Digestible and indigestible
You may have heard of the terms, digestible and indigestible carbohydrates. Digestible carbohydrates include glucose, fructose and galactose that are degraded in the small intestine and released into the bloodstream rapidly as glucose for energy. Indigestible carbohydrates, which are also known as ‘dietary fibre’ include non-starch polysaccharides, lignin, resistant starches and non-digestible oligosaccharides.
These dietary fibres can be sub-categorized based upon their fermentability in the colon or their solubility in water (soluble and insoluble). Fermentable dietary fibres include inulin, pectin, beta-glucan, fructo-oligosaccharides (FOSs) and galacto-oligosaccharides (GOSs) and are water soluble. Non-fermentable dietary fibres including cellulose, hemicellulose, lignin and resistant starch and are insoluble.
Short-chain fatty acids (SCFAs)
When fermentable dietary fibres undergo the fermentation by gut bacteria, this results in increased yield of SCFAs consisting of butyrate, acetate, propionate, and the gases methane and carbon dioxide. The presence of butyrate in the gut is crucial for healthy immunoregulation, as well as regulating gene expression and maintaining tissue barrier function. These SCFAs are involved in a number of other important processes in the body including the absorption of water and salts, decreasing inflammation, maintaining mucosal integrity, stimulating the proliferation and differentiation of epithelial cells and colonic homeostasis. The composition of the intestinal microbiota, in combination with the quantity of carbohydrates consumed, determines the amounts and types of SCFAs available.
The type of protein consumed has a variable effect on the composition of the gut microbiota. Animal-based proteins have been shown to increase the abundance of Bacteroides, Alistipes and Bilophila, which are bile-tolerant anaerobic bacteria that cause an increase of trimethylamine N-oxide (TMAO), which play a role in the pathogenesis of cardiovascular disease by having a proatherogenic effect. The fermentation of animal-based proteins has been shown to result in a decrease in SCFA production and Bifidobacterium abundance, potentially leading to an increased risk of Inflammatory Bowel Disease (IBD).
Plant-based proteins and the fermentation of products like pea and soy protein may stimulate SCFA production by increasing the abundance of Bifidobacterium and Lactobacillus, whilst decreasing Bacteroides fragilis and Clostridium perfringens.
There are three different types of fatty acids that dietary fats are broken down into: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs).
Dietary habits have a strong influence on the composition of the gut microbiota, and the quantity and quantity of dietary fat that is consumed directly influences the composition of the gut microbiota. Dietary sources of fat from animal products mainly contain SFAs. Diets high in SFAs have been shown to result in a decrease in Bacteroidetes and an increase in Firmicutes and Proteobacteria. This has the potential to cause intestinal dysbiosis leading to alterations in intestinal barrier function. High fat diets are associated with an increased abundance of sulphate-reducing bacteria (SRB). Evidence has shown that SRB can cause increased gut inflammation, IBD, colitis and a defective mucus layer.
Lifestyle influences on the gut:
Dysbiosis of the gut is associated with weight gain and obesity. Physical activity, diet and dietary supplementation, medications and bariatric surgery all directly affect the gut microbiome.
Exercise is known to promote improvements in cognition, mood and psychological disorders. In patients with anxiety and depression aerobic exercise has shown to improve symptoms after training. In patients suffering from irritable bowel syndrome (IBS), improvements in mental and emotional wellbeing have been documented following training. Exercise independently improves symptoms of IBS and stabilises the tight-junction barrier which helps to regulate permeability of the intestines. It increases Hypothalamic-Pituitary axis control and decreases symptoms of depression and anxiety.
Priming and maturation of the adaptive immune system is a key function of the gut microbiota. Antibiotic use has been shown to negatively impact multiple aspects of the microbiome including altered metabolic activity, reduced species diversity and recurrent infections (including infection with Clostridium difficile). In adults, combination antibiotic administration can result in increased Enterobacteriaceae, and a decrease in Bifidobacterium and butyrate-producing species.
Antibiotic use in childhood can also lead to conditions affecting the immune system as well as the gastrointestinal and neurocognitive systems. Association have been observed between antibiotic use in childhood and the development of obesity, asthma, allergies and Irritable Bowel Disease in later life. A delay in the development of the gut microbiota has also been observed with antibiotic use in infancy. The specific strains shown to be depleted by antibiotics include Enterobacteriaceae, Lachnosiraceae and Erysipelotrichaeae.
Bacterial strains that comprise the gut microbiome are often present for decades, however abundance of the gut microbiota varies over time and with factors involving diet, lifestyle, co-morbidities, drug intake and colonic transit time. All of these factors have been shown to impact the composition of bacteria found in faecal samples. Changes to microbiota composition may also result from acute infectious diarrhoea and following treatment with antibiotics, however over time this usually returns to its previous state. Antibiotic use can lead to overgrowth of pathobionts (i.e., organisms that can cause harm under certain circumstances) such as C. difficile which can damage the gut mucosa via the production of toxins.
You may have heard of, or even been tested for Helicobacter pylori (H. pylori) infection if you have previously had symptoms of abdominal pain, belly ache or burning, nausea, loss of appetite, frequent burping, bloating or unintentional weight loss. This infection results in an inflammatory response in the gastric mucosa, and in some cases can lead to gastric and/or duodenal ulcers, gastric cancer or intestinal metaplasia. Treatment is with antibiotic use, however eradication of H. pylori can have both positive and negative effects on the microbiota. Whilst eradication will restore the composition of the microbiome in the absence of H.pylori, it can also cause decrease the abundance of Bacteroidetes and increase the abundance of Firmicutes. Increasing the prevalence of bacteria that produce SCFA can lead to an increased risk of metabolic disorders.
As interest and research in gut health continues to grow, we are discovering more about the profound impact that the gut microbiome has on our health. Some gut microorganisms have been shown to have negative influences on conditions like obesity, mood disorders, skin conditions such as psoriasis and mental conditions like autism. The microbiome can also influence the development of certain chronic diseases, ranging from colorectal cancer to metabolic and gastrointestinal diseases.
The influence of the gut microbiome on systemic inflammation has recently been recognised as an important mediator in the development of obesity. As mentioned earlier, the ratio of F/B plays a large role in the homeostasis and overall health of the gut microbiota. Obesity and intestinal inflammation has been linked with an increased ratio of F/B when compared to lean individuals. There have been a number of different studies claiming Firmicutes have a superior capacity to metabolize and ferment carbohydrates and lipids, which contributes to the development of obesity. To help reduce the ratio of F/B, food and probiotic supplementation can help to influence weight reduction and the composition of the gut microbiota. The specifics probiotics showing potential include the genera Lactobacillus and Bacillus as well as the yeast Saccharomyces. We will discuss the role of probiotics in human health in the near future, so stay tuned!
Gut-Brain connection (anxiety/stress)
The gut microbiome is now considered a vital organ and most recently has been called the second brain. This is due to the Enteric Nervous System (ENS), which is an extensive network of cells located along the digestive tract. The ENS provides control of secretion, barrier function and movement of fluid across the epithelium. It also interacts with immune and endocrine systems of the gut, and mediates local blood flow and intestinal motility. The gut releases hormones including neurotransmitters and immunological factors that send signals to the brain . This communication between the gut microbiota and the central nervous system (CNS) is referred to as the gut-brain-axis. Dysbiosis in the gut has been shown to contribute to mental health conditions such as anxiety and depression. The introduction of probiotics into the diet may assist in restoring normal microbial balance, and shows promise in potentially preventing and treating anxiety and depression.
When there is inflammation within the gut, the microbiome is placed under stress by neurotransmitter and cytokine release. This causes increased intestinal permeability which can result in elevated cytokine levels, increasing blood-brain barrier permeability and influencing brain function with some evidence it can contribute to memory loss, depression and anxiety.
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