12.08.2022 Feature Article

How Intestinal Bacteria Help Humans to Stay Healthy.

How Intestinal Bacteria Help Humans to Stay Healthy.
12.08.2022 LISTEN


Gut microbiota refers to a diverse community of microorganisms that colonize the gut mucosa.

Humans are seeded with their first microbes at birth, both on the skin and in the gut.

The initial seeding sets the stage for a person’s developing immune system, influencing the risk for future diseases.

The gut microbiome exists in a state of mutual symbiosis with the human host.

The microbes benefit from the stable and nutrient-rich environment of the gut.

Humans do not possess all the requisite genetic codes for optimal metabolic health promotion.

There are over 100 trillion bacteria in the gut (belonging to about 400 bacterial species). The gut microbiota encodes over three million genes (far greater than the genome in humans) that can produce various metabolites essential for human health.

So, the gut microbiota provides the human host with metabolites that are naturally not produced by humans, but essential for optimal human health.

Metabolites from the gut microbiota:

  • Help human host to develop their immune system.
  • Help regulate host metabolism

  • Modulate host brain functions.
    Dysbiosis is the alteration of the composition of human microbiota at given site. Gut dysbiosis can lead to alteration of the host physiology resulting in the pathogenic processes of different diseases.

    Gut dysbiosis leads to poor gut-health. There is loss of gut integrity and immunity.

    There is upregulation of proinflammatory cytokines and chemokines (due to loss of Regulatory T cell anti-inflammatory activities associated with Gut dysbiosis).

    Gram negative bacteria generate lipopolysaccharides (LPS), a marker of inflammation. Overproduction or abundance of gram-negative bacteria in the gut can cause inflammation

    A Gut dysbiosis induces a chronic state of systemic low-grade inflammation that plays a crucial role in the pathophysiology of chronic diseases. Gut dysbiosis is associated with the following:

    . Cardiovascular diseases (Atherosclerosis, HTN); Metabolic disorders (Type 2 diabetes, Obesity); chronic kidney diseases; Autoimmune disorders, Neurological disorders.

    Association does not mean causality; causality, however, has been demonstrated in rodent models.

    The 2- to 4- short chain fatty acids (SCFAs), mainly, Acetate, Propionate and Butyrate, are generated by bacterial fermentation of dietary fibers and non-digestible carbohydrates.

    The SCFAs are readily absorbed from the large intestines into the bloodstream to reach distant tissues like liver, kidneys, fatty tissues. Acetate readily crosses the Blood-Brain Barrier to reach the brain tissue.

    The production of SCFA is influenced by the pattern of food intake and diet mediated changes in the gut microbiota.

    The SCFAs are involved in cellular energy production and are known to affect Lipids, Glucose, Cholesterol metabolism.

    The SCFAs improve insulin sensitivity and therefore, support the role of the gut microbiota in glycemic control.

    About 90-95% of the short chain fatty acids are absorbed from the colon into the systemic circulation (only 5-10% of the short chain fatty acids are lost in stools).

    SCFAs switch gene-expression on and off by inhibiting histone deacetylase (HDAC).

    By so doing, the SCFAs upregulate anti-inflammatory cytokines/chemokines; down-regulate proinflammatory cytokines.

    SCFAs not only protect against diet-induced obesity, but also inhibit insulin resistance (Lin et al., 2012)

    The SCFAs switch on the genetic codes that help to burn body fat as fuel for energy production in the cells.

    SCFAs promote Regulatory T (Treg) cells formation.
    It is the Tregs that suppress the production of inflammatory cytokines by inflammatory T-cells. So, the SCFAs could be described as Anti-inflammatory agents; they help the human body to control inflammations.

    The SCFAs exert regulatory control over the production of enzymes involved in cholesterol generation, and those that promote plaque-formation in blood vessels.

    Butyric acid downregulates de novo lipogenesis, ameliorate lipo-toxicity, slows down atherosclerosis progression, and stimulate the burning of fats as fuel for energy production in the body cells.

    SCFAs modulate brain and behavioral health; they influence maturation and functions of microglia.

    Altered SCFA production has been implicated in a variety of neurobehavioral diseases including Autistic spectrum disorder, and neurodegenerative diseases like Parkinson diseases.

    Gram negative bacteria generate Lipopolysaccharides (LPS). On brain tissue, LPS may activate immune cells to induce inflammatory cytokines that cause low-grade neuroinflammation.

    SCFAs generate anti-inflammatory cytokines that prevent neuroinflammation.

    Elderly persons have impaired barrier functions of both the intestinal wall and the Blood-Brain Barrier.

    Bacterial amyloid and LPS may escape from intestine, into the circulation; enter the brain tissue to promote neuroinflammation that lead to neurodegenerative diseases like Parkinsons diseases, Multiple sclerosis, Dementia.

    A healthy gut microbiome generates the SCFAs. SCFAs affect epithelial-, immune-, nervous-, and vascular functions to modulate blood pressure

    Studies indicate that gut dysbiosis is associated with hypertension:

    . in hypertensive Rats there is a reduction in microbial richness and diversity

    . There is a reduction in butyrate- and acetate-producing bacteria in hypertensives

    . There is an increase in Firmicutes bacteria phyla relative to Bacteroidetes in the gut

    SCFA-receptors are expressed in renal tissues; intestinal dysbiosis activates the renin-angiotensin system (RAS) which contributes to chronic kidney diseases (CKD)

    SCFAs affect blood pressure by modulating local RAS in the kidneys. Butyrate inhibits Ang II-induced hypertension by suppressing the (pro)renin receptor and intrarenal RAS

    SCFA receptors (i.e., Gpr41, Olfr78) in the renal Juxtaglomerular apparatus mediate renin secretion in response from gut microbiota signals to lower baseline blood pressure.

    Western diets (high-protein, high-fat, low-fiber components) and the commercially processed foods promote Gut Dysbiosis and decreased microbial diversity in the gut.

    Western diets, therefore, promote obesity, metabolic syndrome, chronic diseases like cardiovascular diseases, hypertension, and cancers

    The high fructose sugary drinks made from corn syrups promote Gut dysbiosis and, metabolic syndrome.

    High fiber diet serves as fuel for gut microbiome. Gut metabolome including the SCFAs are essential products for optimal gut function. (High protein diets could promote the formation of harmful products in the gut).

    Therefore, a healthy dietary pattern should include high-fiber vegetables like broccoli, spinach (and other green-leafy vegetables), nuts, seeds and whole grains, and fresh farm produce to help maintain gut health.

    Diets high in fiber (low in animal proteins and animal fats) that have been minimally processed are good for gut health. A healthy gut promotes good health and prevents the chronic diseases. Indeed, you are what you eat.