The gut’s microbes: key players in health and disease.

Our gut’s microbes protect us against pathogens, interact with our immune system, with digestion, and synthesise essential vitamins.

The gut’s microbiota.

The gut’s microbiota consists of the trillions of microorganisms - including bacteria, fungi, viruses, and other microbes - that live in our intestines.

Our microbiota is an essential and highly individualized ecosystem. A diverse and stable (“healthy”) gut microbiota helps us to digest and better absorb nutrients. It is associated with stronger intestinal barriers, efficient immune responses, and synthesis of vital nutrients.

Beyond its role in digestion, our microbiota is increasingly recognized as a key player in metabolism, inflammation control, and brain function. Our interactions with our microbiota occur mainly at the GI mucosa.

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). Some of the viruses present in our gut, the bacteriophages, infect and destroy bacteria, playing a key role in determining the microbiota’s bacterial composition.

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 is associated with diseases such as obesity and diabetes. 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.

Dysbiosis may be caused by changes in diet, antibiotics, and lifestyle (e.g., cohabitation with pets, sleep deprivation). Poor diet, antibiotic use, sleep deprivation, and environmental exposure can disrupt microbiota stability.

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

The video (https://youtu.be/NI3KtR3LoqM) reviews various functions of 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.

Diet is a key factor determining the composition of the gut microbiome.

Changes in diet, including in the short term, 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.

Conversely, diets containing highly processed foods with additives (sugars, salt and emulsifiers, antibiotics, and 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. 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 and yeasts that modulate our microbiome-microbiota ecosystem and when taken by mouth can have a beneficial effect on the host. Foods rich in probiotics also provide nutrients, vitamins, minerals, and fibre. They also support the production of essential vitamins such as B12, folic acid, and biotin.

Probiotics show promise in promoting gut, immune, and mental health. Their effectiveness depends on the composition of an individual’s microbiome, as different bacterial strains have distinct functions. Further research is needed to fully understand their potential therapeutic applications in disease prevention and treatment.

Probiotics may support digestive health by modifying the balance of gut microbes, reducing the presence of harmful bacteria, and by producing antimicrobial compounds that help fight infections, and by modulating the body’s immune response.

Probiotics apper to 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.

Kefir with berries.

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.

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).

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.

Prebiotics nourish beneficial gut microbes.

Prebiotics (non-digestible plant fibres that facilitate the growth of healthy gut bacteria) and postbiotics (inactive microorganisms and/or their components that promote health) can also modulate the gut’s microbiome ecosystem.

Prebiotic substances are found in fruits, vegetables, whole grains, and human milk. They may promote the growth of beneficial gut bacteria, particularly bifidobacterium that support gut and brain health. They may 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.

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.

One key question is whether there are broad, non-personalized dietary recommendations that can modulate microbiota-host interactions for improved health across populations.

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.

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.

A 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 brain’s immune cell populations (microglia and peripheral monocytes) are influenced by the integrity of the blood-brain barrier (a cell barrier that lines the brain’s blood vessels regulating the passage of substances from the bloodstream), systemic inflammation, gut permeability, bacterial diversity, microbial metabolites, and overall gastrointestinal function.

A compromised gut barrier, often referred to as “leaky gut,” allows gut-derived substances to enter the circulation abnormally. This can trigger the accumulation of inflammatory signals and immune cells, potentially exacerbating or contributing to the onset of age-related neurodegenerative disorders, such as motor neuron diseases, demyelinating conditions, Alzheimer’s disease, and other proteinopathies.

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 parasympathetic ANS, connects the gut to the brain via its extensive network of nerve branches. Signals from the gut - including information about nutrient availability, microbial activity, and inflammation - are transmitted to the brain. In response, the brain can adjust digestive processes, immune function, and even emotional regulation. Alongside the vagus nerve, the pelvic and spinal nerves also carry sensory signals, including pain and discomfort, from the gut to the brain.

B. The endocrine system, particularly the hypothalamic-pituitary-adrenal (HPA) axis, which governs the body’s stress response, is another key communication pathway. When stress is perceived by the brain, it activates the HPA axis, triggering the release of cortisol, a hormone that prepares the body for action. This stress response impacts the gut as well, altering the composition of gut microbes and increasing gut permeability - changes that can amplify inflammation and contribute to gut dysfunction.

Gut microbes play an active role in this communication network by producing neurotransmitters such as serotonin, dopamine, and gamma-aminobutyric acid (GABA), which influence mood and behavior. They also regulate the release of hormones like glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), which are involved in appetite control and metabolism. Additionally, bacterial metabolites, such as short-chain fatty acids (SCFAs) and tryptophan derivatives, help modulate immune balance, brain function, and neurodevelopment.

C. The immune system is also a crucial component of gut-brain communication. The gut’s abundant immune cells interact with the microbiota to regulate inflammation, protect against infection, and influence mental health. Immune signals, including cytokines and certain neurotransmitters, circulate in the bloodstream and can cross the blood-brain barrier, affecting brain function and influencing mood, cognition, and stress responses.

The brain

and that the gut as the largest immune organ in the body is a critical place for peripheral immune development, “thus influencing brain health.”

Gut microbiota interact with the brain via several mechanisms including microbiota-derived metabolites that enter circulation, direct communication via the vagus nerve, and modulation of the immune system. , Merchak and her coauthors wrote. Leaky gut, they noted, can lead to an accumulation of inflammatory signals and cells that can exacerbate or induce the onset of neurodegenerative conditions.

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.

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.

Foods that promote dietary diversity 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 (parmesano, 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 and omega-3s (reduce inflammation, support the 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.