The Gut’s Microbiota and Microbiome.
The Gut Microbiota: A key player in health and disease.
The microbiota and microbiome protect against pathogens, interact with the immune system, with digestion, and synthesise essential vitamins.
Trillions of microorganisms - including bacteria, fungi, viruses, and other microbes - live in our intestines, forming the gut microbiota. It is an essential and highly individualized ecosystem. A diverse and stable healthy gut microbiota aids our digestion and provides for better nutrient absorption. It is associated with stronger intestinal barriers, efficient immune responses, and synthesis vital nutrients. Beyond its role in digestion, the microbiota is increasingly recognized as a key player in metabolism, inflammation control, and brain function.
Gut microbiota composition develops and evolves from infancy, shaped by diet, genetics, environment, medication use, and overall health. Diversity and stability continually increase throughout early development, reaching a stable and characteristic composition as we age. An individual’s characteristic gut microbiota ecosystem depends both on the host (ingested food, medication and toxins) and the host’s health (e.g., diabetes, obesity).
Microbiota has been implicated in human health and disease.
In good health, our relationship with the gut microbiota is mutually beneficial. We provide a suitable environment for our microbiome to thrive, and in return, it supports our immune function, strengthens intestinal barriers, and supplies essential nutrients, including vitamins and short-chain fatty acids (SCFAs).
The SCFAs, produced exclusively by the microbiome through the fermentation of indigestible dietary fibers, serve as a primary energy source for gastrointestinal (GI) cells while also maintaining gut barrier integrity and immune function. The gut, as the body’s largest immune organ, plays a crucial role in defense mechanisms.
A balanced microbiome also regulates intestinal barrier permeability, controlling the passage of substances from the gut across the digestive epithelium into the bloodstream, ensuring immune protection and overall gut health.
Conversely, changes in microbiota (“dysbiosis”) and its function may cause disease such as obesity and diabetes. Dysbiosis may be caused by changes in diet, antibiotics, and lifestyle (e.g., cohabitation with pets, sleep deprivation). Dysbiosis has also been associated with autism and schizophrenia, neurological diseases, inflammatory bowel disease, cardiovascular disease, and colorectal cancer. Despite the evident association of gut dysbiosis with these diseases, it is still largely unknown whether dysbiosis promotes or is a cause of these diseases.
See:
https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-1705-z
https://news.cnrs.fr/articles/the-little-known-powers-of-our-gut-microbiota
This video (https://youtu.be/NI3KtR3LoqM) reviews various functions of our gut microbiota (downloaded from: CSRIO, Commonwealth Scientific and Industrial Research Organisation, Australia).
The Microbiota as a “Second Genome.”
The human gut microbiota possesses a collective genome known as the gut microbiome (gut microbiome refers to the functional and genetic characteristics of the microbiota). It has ~ 3 million genes, vastly outnumbering our ~ 20,000 protein-coding genes. This enables the microbiota to function as a “second genome,” producing essential compounds that we cannot synthesize on our own, including vitamins such as B12, biotin, folic acid, and short-chain fatty acids (SCFAs) such as butyrate. SCFAs also serve as an energy source for gut cells, strengthen the gut and blood-brain barriers, and help regulate immune function.
The gut microbiota has an essential role producing compounds that influence immune function and central the nervous system (CNS). The immune system acts as a communication mediator, with innate immunity providing the first line of defence and adaptive immunity fine-tuning responses.
Gut microbes can influence both gut and brain function by producing and also modifing the composition of butyrate and other SCFAs that contribute to neurogenesis and microglia regulation in the brain.
Gut dysbiosis and disease.
Imbalanced gut microbiota (dysbiosis) can contribute to metabolic, inflammatory, and neurological disorders. Conditions linked to dysbiosis include obesity, diabetes, inflammatory bowel disease (IBD), cardiovascular disease, autism, and schizophrenia.
Factors such as poor diet, antibiotic use, sleep deprivation, and environmental exposure can disrupt microbiota stability.
The microbiome-microbiota ecosystem composition and stability are modulated by genetics, age, geography, medication, and very importantly through what we eat. Greater microbiome diversity is healthy. Our interactions with our microbiome occur mainly at the GI mucosa.
Diet is a key factor determining the composition of the gut microbiome.
Even short-term changes in diet have been shown to change our gut microbiome. Fortunately, the microbiome is relatively resistant to long-term changes and will typically return to its original composition after short-term dietary changes, antibiotic treatment, or an acute invasion by a pathogenic microorganism. However, short-term microbiome changes may interrupt normal metabolite production. This in turn may cause changes in the host’s gene expression that could lead to more long-lasting effects. Manipulation of an individual’s gut microbiota by changing food patterns may be a powerful means to modulate human health.
Diets rich in nutrient-dense, whole foods support the growth of beneficial microbiota that promote health. Dietary antioxidants reduce gut microbiota inflammation, manipulate its microbial composition, the integrity of the intestinal mucosal barrier, the production of short -chain fatty acids (SCFA) and their effects on the immune system.
Probiotics are live bacteria and yeasts that taken by mouth that modulate our microbiome-microbiota ecosystem. They are defined as "live biotherapeutic products" or “medicinal products containing live micro-organisms such as bacteria or yeasts for human use” that can have a beneficial effect on the host when administered in sufficient quantities. Foods rich in probiotics also provide nutrients, vitamins, minerals, and fibre, together with pre-biotics (plant fibres that facilitate the growth of healthy gut bacteria) and post-biotics (inactive microorganisms and/or their components that promote health).
Conversely, diets containing highly processed foods with additives (sugars, salt and emulsifiers, antibiotics, others) promote gut microbes that are linked to cardiovascular and metabolic disease.
Recent studies indicate that high-fibre diets and fermented-food diets can change microbiome function. Altering dietary fibre intake by increasing total carbohydrates, whole grains, and resistant starches has shown significant impacts on the microbiota accompanied by improvements in health markers (e.g., ). Indeed, the microbiota-accessible carbohydrates (MAC) present in dietary fibre act to support gut microbiota diversity and metabolism. SCFA, a product of fibre fermentation by the gut microbiota, maintain gut barrier health and attenuate inflammation. Boosting fibre intake could therefore be a powerful way to modulate the human immune system via the microbiota.
Probiotics and their impact on health
Probiotics are live bacteria that support gut health and apper to also influence brain function through the microbiome-gut-brain axis. A specialized group of probiotics, known as psychobiotics, may help improve mood, cognition, and stress response.
Certain probiotic strains, particularly Lactobacillus and Bifidobacterium, have been linked to improvements in anxiety, depression, and inflammation. Studies have shown that Lactobacillus casei (found in our gut, in fermented foods, and yogurt, kefir, and some cheeses) improved mood in elderly individuals, while a combination of Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum (found in our gut, mouth, and breast milk) reduced both depression symptoms and inflammation in people with major depressive disorder. Bifidobacterium longum (found in the gut) has been found to help with depression in individuals with irritable bowel syndrome, though it did not affect anxiety levels. Similarly, Lactobacillus plantarum (human gut and fermented foods such as sauerkraut, kimchi, sourdough bread, and yogurt) was shown to reduce stress, but it had no significant impact on inflammatory markers.
Probiotics have also been studied in the context of autism spectrum disorder, where Bifidobacteria and Lactobacilli have demonstrated potential benefits in animal studies. Human studies suggest that Lactobacillus acidophilus, Lactobacillus rhamnosus, and B. longum may offer behavioral improvements, though research remains inconclusive. In schizophrenia, probiotics have shown limited psychiatric benefits but may help reduce gut inflammation and support immune function. Some studies indicate that supplementation with Lactobacillus rhamnosus and Bifidobacterium animalis lowered inflammation-related proteins, while Bifidobacterium brevewas associated with improvements in anxiety and depression symptoms in certain patients. However, more research is needed to confirm these effects.
Beyond mental health, probiotics and fermented foods such as yogurt, kombucha, and kimchi have been linked to lower risks of diabetes, cardiovascular disease, and cancer. A study on a fermented-food diet showed an increase in gut microbiota diversity along with a reduction in inflammation markers.
Probiotics may also support digestive health by modifying the balance of gut microbes, reducing the presence of harmful bacteria, producing antimicrobial compounds that help fight infections and modulating the body’s immune response. reducing harmful organisms in the intestine, producing antimicrobial compounds (substances that destroy or suppress the growth of microorganisms) and Additionally, they play a role in regulating the immune system, aiding digestion, and supporting the production of essential vitamins such as B12, folic acid, and biotin.
The effectiveness of probiotics depends on the composition of an individual’s microbiome, as different bacterial strains have distinct functions. While probiotics show promise in promoting gut, immune, and mental health, further research is needed to fully understand their potential therapeutic applications in disease prevention and treatment.
Kefir with berries.
The potential beneficial effects of probiotics administration are dependent on the structure and function of the host microbiome.
Fecal transplants meet the definition of a probiotic when used as a treatment for recurrent C. difficileinfection (a type of gastrointestinal infection).
Prebiotics nourish beneficial gut microbes.
Prebiotics are non-digestible dietary compounds that promote the growth of beneficial gut bacteria, particularly Bifidobacterium, supporting gut and brain health. Found in fruits, vegetables, whole grains, and human milk, prebiotics help balance the microbiome-gut-brain axis and may influence mental well-being.
Among the most studied prebiotics are fructooligosaccharides (FOS) and galactooligosaccharides (GOS), which have been shown to modulate gut microbial composition and reduce stress responses. Research indicates that three weeks of GOS supplementation lowered cortisol levels in healthy individuals, suggesting reduced stress, although it did not affect biological markers of inflammation or mental health. Another study found that GOS reduced anxiety symptoms in patients with irritable bowel syndrome (IBS), linking prebiotics to both gut and mood regulation. A separate study in overweight adults showed that a 14-day high-dose prebiotic intervention altered brain activity related to food decision-making, alongside gut microbiota shifts, suggesting a connection between prebiotics and neural processes linked to eating behavior.
Preclinical research further supports the antidepressant-like effects of prebiotics. In a mouse model of autism spectrum disorder (ASD), a diet enriched with FOS/GOS normalized gut bacteria, improved gut barrier function, reduced neuroinflammation, and enhanced social behavior and cognition. Another study found that prebiotics lowered corticosterone (a stress hormone) and increased brain-derived neurotrophic factor (BDNF) in the hippocampus, a key regulator of mood and cognitive function. These findings suggest that prebiotics may influence neurobiological pathways relevant to neuropsychiatric conditions, though human studies remain limited. Further research is needed to clarify the therapeutic potential of prebiotics for mental health.
Kimchi, a probiotic, is a spicy Korean fermented side dish made from vegetables, typically cabbage (above). It is usually flavoured with a blend of chili, garlic, ginger, and scallions. It contains lactic acid forming bacteria reported to benefit gut health (mainly lactobacillus kimchii).
One key question is whether there are broad, non-personalized dietary recommendations that can leverage extant microbiota-host interactions for improved health across populations. Currently the evidence supports this.
See: BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k2179
The Microbiome-Gut-Brain Axis
The microbiome-gut-brain axis is a complex network linking gut bacteria with the brain. It communicates through immune signals, neurotransmitters, and metabolic pathways.
The interaction between the gut, brain, and immune system is dynamic and constantly adapting to environmental signals like diet, stress, and microbial changes. Disruptions in this system have been linked to conditions such as anxiety, depression, neurodegenerative diseases, and autoimmune disorders. Research suggests that modulating the microbiome through diet, probiotics, and lifestyle interventions could help restore balance and improve both mental and physical health.
This growing understanding of the microbiome-gut-brain axis reveals how interconnected our body systems are, with gut health playing a crucial role in brain function, immunity, and overall well-being.
The microbiota influences neurological development and behaviour.
The absence of healthy gut microbiota in germ-free mice interferes with their normal social interactions. These mice, raised in sterile environments without exposure to microbes, exhibit changes in social behaviour, including increased fear and agitation, and prefer to isolate rather than to socialise with other mice. When they do socialise, germ-free mice prefer to do so with new mice introduced into their environment rather than mice they already know. They also have more repetitive behaviours than normal mice.
Gut-brain communication: the Microbiome-Gut-Brain Axis.
The gut and brain are in constant communication through a complex network of nerves, immune pathways, and biochemical messengers. This system, known as the microbiome-gut-brain axis, relies on multiple communication routes, including the autonomic nervous system (ANS), the immune system, and the endocrine system.
A. The vagus nerve, part of the autonomic nervous system, connects the gut with the brain via its nerve branches. Signals from the gut, such as nutrient availability, microbial activity, and inflammation, are transmitted to the brain. In response, the brain can adjust digestion, immune function, and emotional regulation. Alongside the vagus nerve, the pelvic and spinal nerves carry sensory signals, including pain, from the gut to the brain.
B. The endocrine system, particularly the hypothalamic-pituitary-adrenal (HPA) axis that controls the body’s stress response is another important communication pathway. Stress, perceived by the brain, triggers the release of cortisol, a hormone that prepares the body for action. This stress signal also affects the gut, altering microbial composition and gut permeability, which can further amplify inflammation and gut dysfunction.
Gut microbes contribute to this communication by producing neurotransmitters like serotonin, dopamine, and GABA, which regulate mood and behavior. They also modulate the release of hormones like glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), which control hunger and metabolism. Some bacterial metabolites, such as short-chain fatty acids (SCFAs) and tryptophan derivatives, affect immune balance, brain function, and neurodevelopment.
C. The immune system is also crucial for gut-brain communication. The gut’s many immune cells interact with microbes regulating inflammation, infection responses, and mental health. Immune signals, such as cytokines and neurotransmitters, can travel through the bloodstream and affect brain function, influencing mood, cognition, and stress responses.
A balanced diet for gut health.
A diverse diet rich in fiber, prebiotics, probiotics, and nutrient-dense foods helps maintain a balanced gut microbiota and supports overall well-being. These foods that promote dietary diversity, fiber intake, and gut health:
1. Fiber-rich foods (prebiotic sources):
• Vegetables: artichokes, asparagus, onions, garlic, leeks, leafy greens, bell peppers, carrots, cauliflower, Brussels sprouts
• Fruits: apples, bananas, berries, pears, oranges, kiwis, pomegranates
• Legumes: lentils, chickpeas, black beans, kidney beans, peas
• Whole grains: oats, quinoa, brown rice, bulgur, whole wheat, barley
• Nuts and seeds: almonds, walnuts, flaxseeds, chia seeds, sunflower seeds
2. Fermented and probiotic-rich foods.
• Dairy-based: yogurt (with live cultures), kefir, aged cheeses (Parmesan, gouda)
• Non-dairy: sauerkraut, kimchi, miso, tempeh, natto, kombucha, fermented pickles (without vinegar).
3. Resistant starch foods (support gut flora).
• Cooked and cooled potatoes (potato salad), green bananas, cooked and cooled rice, oats.
4. Healthy Fats & Omega-3s (Reduce Inflammation & Support Gut Barrier)
• Fatty fish (salmon, sardines, mackerel), extra virgin olive oil, avocado, walnuts.
5. Polyphenol-rich foods (support microbial diversity and reduce inflammation)
• Dark chocolate (85%+ cocoa), green tea, coffee, red wine (moderation), berries, nuts.
6. Bone broth and collagen sources (support gut barrier and reduce inflammation)
• Bone broth, gelatin, collagen-rich cuts of meat
Key habits for a healthy gut microbiota:
1. Eat a varied diet with a mix of plant-based and fermented foods.
2. Consume fiber daily to nourish beneficial gut bacteria.
3. Limit processed foods, sugar, and artificial sweeteners that may disrupt microbiota balance.
4. Stay hydrated to support digestion and microbial activity.
5. Manage stress through mindfulness, exercise, and quality sleep, as stress affects gut health.