Have you ever wondered about the connection between health and the gut microbiome? Your gut contains trillions of microbes including bacteria, fungi and viruses that are linked to a wide range of health benefits including improved digestion, immune system function and mental health.
What is the gut microbiome and what is the gut microbiota?
- The gut microbiota: the name for the collective microbes living in the digestive system. i.e. the BUGS
- The gut microbiome: the name for all the microbes and their genomes (entire collection of genes) that live in the digestive system, i.e.. the BUGS and their GENES
These commensal bacteria play an essential role in our health. They help break down food, produce vitamins, short chain fatty acids, and other chemicals that can promote health or disease i.e. they are pro-inflammatory. They also can protect against infection and colonization with harmful bacteria.
However each part of the digestive tract such as the oral cavity, stomach and small intestines also have their own unique microbiota and microbe load. The least bacteria is found in the acidic stomach, with increasing numbers in the small intestines and largest numbers in the colon.
Approximately 80 percent of bacteria are unable to be grown in culture medium so it is only since advances in DNA sequencing technology that we have had an explosion of information about the human gut microbiome
The adult human intestinal microbiota is dominated by only two phyla, Bacteroidetes and Firmicutes, but also has smaller amounts of Proteobacteria, Verrucomicrobia, Actinobacteria, Fusobacteria and Cyanobacteria. On a species and strain level, individuals have significant variability between microbiota so that each persons microbiota is unique, like a fingerprint. Despite the microbial diversity in species and strains the research suggests that individuals in health maintain a functional core of bacterial genes i.e. the core gut microbiome.
Enterotypes of the Human Gut Microbiome
In a cross-culture and continent study published in Nature in 2011 there appears to be 3 enterotypes or 3 gut microbiota-types;
- Enterotype 1 – Bacteroides dominated – this cluster can lack diversity. it is likely to reflect the Western diet and eating habits.
- Enterotype 2 – Prevotella driven – this cluster is common for high-fiber whole-food diets with grains, pulses, vegetables and fruit, or people who consume refined carbohydrates like sweets and pastries.
- Enterotype 3 – Ruminococcus enriched-tends to be associated with a diet rich in dietary fibre and resistant starches.
However future research will determine how universal these enterotypes are and their specific relationship to health.
How the gut becomes colonized with microbes
The human gut becomes colonized with microbes initially in utero, via the birthing process and through early feeding. A systemic review from 2021 suggests that gut colonization is a dynamic process during the first 36 months of an infants life. After this point the gut microbiota becomes more stable and ‘adult-like’.
The mode of delivery, vaginal or caesarean section, has an impact on the gut microbiota. Studies have shown that babies born vaginally have a gut microbiota more similar to their mothers than babies born by C-section, which have guts that are more colonized with skin bacteria than vaginally born infants.
Babies who are fed formula milk have a gut microbiota composition that is different from babies who are breastfed. One study in 2020 found that breast fed babies had higher Bifidobacterium and Bacteroides and lower Streptococcus, Enterococcus, Veillonella and Clostridioides in their gut microbiota compared with formula fed babies.
Another study published in BMC Pediatrics in 2020 found infants born by caesarean had lower Bifidobacterium, but interestingly, when infants who were born via caesarean are breast fed, their gut microbiota is restored to a microbiome that resembles a vaginally born infant and they have a similar lower risk of infections in early life.
The composition of an individuals gut microbiota is also influenced by diet, age, health status, medication use and other factors.
Why are gut bacteria important for health?
The human gut microbiota acts as a metabolic organ in the human body. This is incredible – we have a nonhuman organ metabolizing nutrients and performing many functions essential for our health!
The healthy human microbiome performs the following essential roles:
The microbiota help break down complex indigestible carbohydrates, fiber and protein which the human body cannot digest on its own. They also produce short chain fatty acids (acetate, propionate and butyrate) which have a beneficial effect on the intestinal epithelial cells and can be used by colonocytes (colon cells) for energy.
The gut microbiota can synthesize amino acids and short chain fatty acids.
Isoflavones are metabolized into active compounds by the gut microbiota and they conjugate (or add amino acids to) bile acids. The microbiota also activates bioactive compounds including phytoestrogens.
When lipids (fats) are consumed in the diet, the gut microbiota influences the absorption, storage and metabolism of these fats.
Immune system function
The gut microbiota help to train and develop the immune system. A healthy gut microbiota is thought to be important for preventing allergies and autoimmune diseases. Butyrate (produced by the microbiome) is used by colon cells to induce mucin secretion, trefoil factors and antimicrobial peptides.
It also is involved in immune modulation of cell cycle inhibition by inducing programmed cell death and cell differentiation – an essential role for inhibition of cancerous growth. Butyrate and propionate also promote Treg cell differentiation. Treg cells are essential for suppressing inflammatory response.
The gut microbiota has been linked to a number of mental health conditions including depression, anxiety and autism. This occurs via exportation of microbiota-derived metabolites via the blood circulation to the brain or via the gut-brain-axis. The gut microbiota has direct impact on brain health via both neuroendocrine and metabolic pathways (Carabotti et al, 2015)
The intestinal microbiota is able to transform carcinogenic compounds such as N-nitroso compounds (NOCs) and heterocyclic amines (HCAs). It is also involved in the detoxification of drugs, so the composition of the microbiota can influence how effective medical treatments can be.
What are the consequences of an unhealthy gut microbiota?
An unhealthy gut microbiota has been linked to a number of diseases. Elie Metchnikoff (1845-1916), Russian immunology and probiotic pioneer, suggested that most disease begins in the digestive tract when the “good” bacteria are no longer able to control the “bad” bacteria.
He called this condition dysbiosis. Dysbiosis is an ecosystem where bacteria no longer live together in mutual harmony (Iebba et al, 2016).
Gut microbiota dysbiosis can consist of the following issues:
- reduced variety of the gut microbiota or
- increased levels of gut bacteria associated with disease or
- lower levels of bacteria associated with health.
Gut dysbiosis is associated with many human diseases including; autoimmune and inflammatory diseases
Eubiosis is where gut microbiota has an abundance of beneficial species, belonging mainly to the two bacterial phylum Firmicutes and Bacteroides, while potentially pathogenic species, such as the phyla Proteobacteria (Enterobacteriaceae) are present, but in low proportions.
Regulation of the human gut microbiome: What factors influence the gut microbiome?
Diet and the gut microbiota
Diet has emerged in the research literature as the strongest factor regulating the structure and the function of the gut microbial community (Cady et al, 2020). People who live in unindustrialized rural communities have a higher abundance of bacteria that is rich in enzymes capable of digesting plant-based complex polysaccharides.
These healthy microbiome-associated diets are rich in fiber and fermented food. They establish a diverse microbiome and produce vital metabolites.
Individuals who live in industrialized communities and nations and consume a standard western diet rich in animal protein, fats and refined/simple sugars i.e. sugar and flour is enriched with gut bacteria containing enzymes responsible for metabolism of simple sugars, amino acids and bile acids.
These industrialized diets which are high in fat, animal proteins and simple carbohydrates increase gut dysbiosis in infants and adults and contribute to chronic inflammation, chronic disease and reduced ability to cope with acute infection.
People who consume the typical western industrialized diet have lower levels of Firmicutes phyla, Bifidobacterium and Eubacterium species and higher levels of Bacteroides and Enterobacteria. They also have altered gut microbiota that are higher producers of cancer-promoting nitrosamines. This dysbiosis has been associated with obesity, insulin resistance and type 2 diabetes.
Bifidobacterium and Eubacterium species can be increased by converting to a plant-fiber rich diet such as the Mediterranean diet (Singh et al, 2017).
There are a variety of other environmental factors that influence the gut microbiota including many medications, environmental toxins, alcohol and cigarette smoking, artificial sweeteners, physical exercise and stress.
Many medications have an impact on the gut microbiota. A study published in 2020 showed the medication groups that have the greatest impact on the human gut microbiome include; proton pump inhibitors, metformin, antibiotics and laxatives.
Proton pump inhibitors (PPIs) such as omeprazole and lansoprazole inhibit acid production in the stomach. This has the role of both providing antimicrobial effects in the stomach and moderating the pH in the upper GI tract.
Of all medications, PPI use shows the greatest change in both number of bacterial species and altered microbial pathways.
Use of PPI promotes the growth and proliferation of oral bacteria in the stomach. It also directly inhibiting the growth of bacterial species Dorea and Ruminococcus.
Their use is also associated with an increased number of gut infections caused by pathogenic gut bacteria: Clostridium difficile, Salmonella spp., Shigella spp and Campylobacter spp.
Metformin use has been found to be associated with changes in the metabolic potential of the microbiome. There are increases in butyrate production, quinone biosynthesis, sugar derivative degradation and polymyxin resistance pathways.
These metabolic pathways appear to be facilitated by E.coli and suggest that metformin offers a metabolic advantage to the microbiome.
Antibiotics are medications have antimicrobial effects usually taken to treat life-threatening infectious disease. However they do not select for specific bacteria so can decimate entire populations of gut microbiota.
Often after antibiotic treatment, gut dysbiosis can occur with bad bacteria proliferating faster than good bacteria. Partial recovery can occur for some, however others develop long term reduction in gut microbiome diversity and dysbiosis.
Laxative use showed a higher abundance of Alistipes and Bacteroides species in their microbiome. These species are part of the core gut microbiome in humans. However when these species are out of balance they are associated with gut dysbiosis and emerging connections to inflammation, cancer and mental health conditions (Parker et al, 2020).
However laxatives can change transit time, and can be varied in mechanism. Some laxatives like lactulose are actually a prebiotic so further research to delineate which laxatives have negative and positive effects on the microbiome is needed.
Environmental toxins and the gut microbiota
There are many environmental toxins that have an impact on the gut microbiota. These include;
- diethylstilbestrol (DES),
- persistent organic pollutants (POPs)
- triclosan – an antimicrobial found in toothpaste
- and air pollution (Tu et al, 2020)
Of note the shikimate pathway, the target of herbicide glyphosate, is commonly present in human gut bacteria and inhibited by glyphosate coated foods.
Artificial sweeteners and gut microbiome
Many artificial sweeteners are generally regarded as safe (GRAS) as they are poorly metabolized by the body, however the actions and impacts on the microbiome were not considered when these substances were approved. Some sweeteners such as steviosides and xylitol are metabolized by the gut microbiome. Artificial sweetener use impacts on the microbiome, producing a dysbiotic intestinal gut flora and elevated inflammatory levels. Other artificial sweeteners have been implicated in increased production of bacterial metabolites that have negative health implications including obesity.
Tobacco and alcohol and the microbiome
Alcohol consumption leads to reductions in Firmicutes, especially Clostridium species and lactobacillus and increases in Bacteroidetes and Proteobacteria phylum – especially the Enterobacteriaceae family (Engen et al, 2015). There is also an alteration in the metabolic pathways associated with ethanol metabolism, amino acid and carbohydrate metabolism. All these effects lead to a dysbiosis which can persist even after alcohol consumption has ceased.
Dysbiosis gut bacteria induced by alcohol use can result in
- increased GIT inflammation
- intestinal hyperpermeability resulting in endotoxemia
- systemic inflammation
- tissue damage/organ damage.
Tobacco smoking introduces a variety of chemical compounds into the body via the lungs including nicotine, heavy-metals, aldehydes, volatile organic compounds and polycyclic aromatic hydrocarbons (Gui et al, 2021). These chemical have been found to be associated with increases in Enterobacteriaceae, Proteobacteria and Actinobacteria in the gut. There is also an alteration in the metabolic pathways associated with nicotine metabolism and cholesterol biosynthesis. Smokers also have altered oral cavity and lung microbiotas (Huang et al, 2019). These dysbiotic changes can persist even after smoking has ceased.
Exercise and the gut microbiome
Exercise has been found to have a number of benefits for gut health. These include;
- increased production of short chain fatty acids (SCFAs),
- increased levels of IgA and other immune cells,
- increased gut barrier function
- improved gut motility.
- changes in the composition of the microbiome, with an increase in Firmicutes and a decrease in Proteobacteria. These changes lead to more bacterial diversity and a healthier microbiome.
Exercise training alters the composition and functional capacity of the gut microbiota, independent of diet (Mailing et al, 2019). This means if you begin exercise training in addition to altering your diet to promote a healthy microbiome you will have synergistically positive effects on the diversity and function of your gut microbiome, which in turn has multiple positive effects on health.
A study published in Gut in 2014 showed that the microbiome of rugby players had a relative abundance of 40 different bacterial taxa compared with the gut microbiota of lean sedentary controls.
Likewise a study of active women who exercised at least 3 hours per week had increased levels of Faecalibacterium prausnitzii, Roseburia hominis, and Akkermansia muciniphila compared with inactive controls.
F. prausnitzii and R. hominis are butyrate producers, whereas A. muciniphila is associated with a lean body mass index (BMI) and improved metabolic health.
How the Gut Microbiome Affects the Body in chronic disease
There are a variety of mechanisms whereby gut microbiota dysbiosis contribute to disease in the body, and the diseases they influence are not limited to diseases of the gut. The gut microbiome, through their metabolites and cell wall properties impairs health and cause inflammatory disease in many parts of the body including skin, joints, brain and pelvic organs.
The dysbiotic intestinal bacteria produce metabolites that are either toxic or inflammatory. Dysbiotic gut microbiota can also cause alterations in the gut barrier (intestinal barrier) that allows bacteria and their toxins to translocate into the bloodstream.
This is known as increased intestinal permeability or commonly called ‘leaky gut’. It also enhances the transport of inflammatory metabolites through the bloodstream. These substances also can recruit the immune system to contribute to ongoing inflammation in the affected organ.
Some metabolites of intestinal microbial metabolism that are linked to disease include;
- lipopolysaccharide (LPS),
- short chain fatty acids (SCFAs),
- hydrogen sulfide,
- amines and
- trimethylamine N-oxide (TMAO).
Lipopolysaccharide is a bacterial toxin. It is a component of the cell wall of Gram-negative bacteria such as . LPS can cause inflammation when it translocates from the gut into the bloodstream.
SCFAs are fermentation products of dietary fibre that are produced by gut bacteria. SCFAs can have both anti-inflammatory and pro-inflammatory effects depending on the type of SCFA and the concentrations present.
Ammonia is a by-product of protein metabolism that is toxic at high concentrations.
Hydrogen sulfide is produced by certain gut bacteria and is also toxic at high concentrations.
Phenols, quinolones, indoles and amines are all metabolites that can have either toxic or pro-inflammatory effects.
Trimethylamine N-oxide: Some bacteria within the gut microbiome convert choline and L-carnitine, found in red meat and other animal-based foods, to trimethylamine (TMA), which is further metabolized to trimethylamine N-oxide (TMAO) in the liver (Tu et al 2020). TMAO levels are highly correlated with cardiovascular disease risks (Wang et al, 2011).
N-nitroso compounds and polyamines: These metabolites are products of protein fermentation by gut bacteria. They exert carcinogenic effects and promote cancer in the colon (Louis et al, 2014)
What diseases are associated with gut microbiome dysbiosis?
It is becoming increasingly clear that many of the chronic inflammatory diseases of modern life are associated with gut microbiome dysbiosis. Here is a non-exhaustive list of some diseases associated with the microbiome and gut dysbiosis:
- Inflammatory bowel disease – ulcerative colitis and Crohn’s disease (Glassner et al, 2020)
- Heart disease (Zhao et al, 2021)
- Obesity (Aoun et al, 2020)
- Diabetes (Sikalidis et al, 2020)
- Metabolic syndrome (Dabke et al, 2019)
- Parkinson’s disease (Romano et al, 2021)
- PCOS (Tremellen et al, 2012)
- Endometriosis (Khan et al, 2018 + Ser et al, 2021 + Laschke et al, 2016)
- Chronic kidney disease (Hobby et al, 2019)
- Eczema (Lee et al, 2018)
- Colon cancer (Jahani-Sherafat et al, 2018)
- Liver diseases – Alcoholic fatty liver disease and non-alcoholic fatty liver disease -NAFLD (Betrapally et al, 2017)
- Celiac disease (Marasco et al, 2016)
- Irritable bowel syndrome (IBS – Menees et al, 2018)
- Chronic fatigue syndrome (König et al, 2022)
- Severity of Covid-19 infection (Yeoh et al, 2021) and Long-covid-19 (Liu et al, 2022)
How can I make my gut microbiome healthy?
If you want to increase your gut microbial diversity + reduce ‘bad’ gut bacteria, these are some ways you can change or cultivate a healthy microbiome or establish eubiosis:
Plant-Based Diet for healthy gut bacteria
You can boost healthy gut bacteria with plant-based foods. A plant-based diet can improve health and prevent disease by feeding the good bacteria in your digestive tract, encouraging microbiota diversity and providing plentiful colonic foods and prebiotics. Eat a wide variety of colorful plant foods and fibers every day including;
- legumes: beans, peas and lentils
- cruciferous vegetables
- green leafy vegetables
- alliums: onions, garlic, shallots
- root vegetables:
- fermented vegetables such as sauerkraut and kimchi
For a healthy microbiome minimize food and drinks that impairs your gut bacterial diversity and to discourage proliferation of harmful bacteria;
- animal protein – especially processed meats
- sugar and flour based foods
- processed foods
- sugary drinks – soda, juices, energy drinks
Probiotic supplementation can be considered- although this alone cannot replace a fiber-rich plant-based diet.
Consider a prebiotic supplement – FOS, GOS or lactulose are effective prebiotics.
Keep things moving by eating plenty of fiber and drinking enough water every day – aim for at least 2 liters (67 fl oz.) daily.
Exercise regularly – regular exercise will start to change your microbiome in ways that reduce inflammation and produce health promoting metabolites such as butyrate. Studies have shown that these changes are present in as little as 5 weeks.
Get enough sleep – getting enough sleep and sufficient quality sleep is important in shaping human gut microbiota diversity (Smith et al, 2019).
Avoid environmental toxins including alcohol and unnecessary medications which reduce the gut microbial diversity and balance.
For people with severe disease sometimes clinicians recommend faecal microbiota transplantation. This is the direct transference of stool, which contains their fecal microbiota, from a healthy donor into the bowel of a patient with intestinal dysbiosis and disease.
We hope you now have a better appreciation of how closely linked health and the gut microbiome are, and how you can influence your gut microbiome for the better.
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