GUT MICROBIOTA AND METABOLIC PROCESSES

Somehow, I predicted that my piece last week on gut microbiota and health was going to surprise many. I think I under estimated the response judging from the feedbacks so far. Therefore, I have little option than to continue with more effects of the gut microbiota, which as indicated in my piece last week, is now an area of intense research. Some of the feedbacks have been from students and workers in related fields of practice so permit me, dear reader, for the extent I may have to go this time round.

I used materials from a paper by Belizario et al titled “Gut Microbiome Dysbiosis and Immunometabolism: New Frontiers For Treatment of Metabolic Diseases”. It is published in Mediators of Inflammation.Vol 2018. Article ID 2037838.

It noted that the gastrointestinal (GI) tract possessed its own nervoussystem known as the enteric nervous system. This systemcommunicated with the central nervous system throughnerves, such as the vagus, neuromodulators, and neurotransmittersof sympathetic and parasympathetic branches of theautonomic nervous system. What many might not know was that bacterial richness and diversityin the gut microbiota occupied a central role in normalmetabolic and immunological functions of tissues and organs.

Microorganisms in the gut performed their functions largely through enzyme pathways, in order to digest complex dietary carbohydrates and proteins. Gut microbiota provided the branched-chain amino acids leucine, isoleucine, and valine, and particularly glycine, which was required for the synthesis of glutathione. Glutathione was the main intracellular antioxidant and detoxifying agent necessary for many biological functions of the host.

 Bacteria of the gut synthesized a large variety of signaling molecules of low molecular weight that included methane, hydrogen sulfide, and nongaseous metabolites. These products were able to turn on or off both host genes and microbe virulence and metabolism genes. Anytime you are tempted to use antibiotics inappropriately, for example, just think about the effects this could have gut microbiota.

The gut microbiota also sensed diverse environmental signals, including host hormones and nutrients, and responded to them by differential gene regulation and niche adaptation. The maintenance of a stable, fermentative gut microbiota required diets rich in whole plant foods, particularly rich in fibers. Again, one of the key reasons to have high fiber content as part of your daily diet. Pure Cocoa powder has a very high fiber content.

These substrates (e.g. fibers)were processed by the intestinal microbiota enzymes, such as glycoside hydrolases and polysaccharide lyases to produce polyamines, vitamins B and K. Under anaerobic conditions, species belonging to the Bacteroides genus, and to the Clostridiaceae and Lactobacillaceae families, produced short-chain fatty acids (SCFAs). SCFAs, volatile fat acids, which were able to cross the blood-brain barrier via monocarboxylate transporters. SCFAs produced by intestinal bacteria are acetate (2 carbon atoms), propionate (3 carbon atoms), and butyrate (4 carbon atoms). Most of SCFAs were metabolized to carbon dioxide (CO₂).

Butyrate acted on cells to provide energy for cellular metabolism. It also regulated apoptosis (programmed cell death), cellular differentiation, and chemical modification of nuclear proteins and nucleic acid.

Acetate and propionate passed into the bloodstream where they were taken up by the liver and peripheral organs, and acted as substrates for gluconeogenesis (production of glucose from non-carbohydrate sources) and lipogenesis (fat storage). The G-protein-coupled receptors (GPRs), GPR41 and GPR43, also named free fatty acid receptors 2 and 3 (FFARs 2/3) present in many tissues, including adipose, gut enteroendocrine cells, and inflammatory cells acted as major receptors of SCFAs. Under certain physiological conditions, SCFAs could induce the secretion of glucagon-like peptides (GLP-1 and GLP-2) and peptide YY (PYY). GLP1 stimulates β cells of the pancreas to produce insulin, whereas PYY inhibits nutrient absorption in the intestinal lumen as well as control the appetite. Again, some of the reasons behind the imbalance in gut  microbiota and development of metabolic disorders such as diabetes.

The gut microbiota contributes to fat deposition through the regulation of the bile acid receptor that is responsible for the regulation of bile acid synthesis, and hepatic triglyceride accumulation. Bile acids, for example, deoxycholic acid, have antimicrobial effects on the gut microbes and also induced the synthesis of antimicrobial peptides by gut epithelial tissue.Furthermore, the gut microbiota regulated directly the bioavailability of choline and indirectly the accumulation of triglycerides in the liver. The gut microbiota also helped the absorption of calcium, magnesium, and iron.

High or low productions of SCFAs, tryptophan metabolites, and neurotransmitters (e.g. GABA, noradrenaline, dopamine, acetylcholine, and 5-hydroxytryptamine-serotonin)were associated with various inflammatory and metabolic diseases and neuropsychiatric disorders. Some of these factors acted as major neurotransmitters and modulators of the brain-gut axis. Serotonin, for example, played central roles in sexuality, substance addiction, appetite, emotions, and stress response.

Thousands of microbiota-derived metabolites with known and unknown functions have been identified as components of the human metabolome. GI microbiota produced large quantities of epigenetically active metabolites, such as folate and A and B vitamins (including riboflavin (B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), folate (B9), and cobalamin (B12)) that regulated the activity of host  enzymes and genetic responses to environmental signals. Therefore, changes in gut microbiota could result in epigenomic changes not only directly in adjacent intestinal cells but also in distant cell lineages, such as hepatocytes (liver cells) and adipocytes (fat cells).

Gut bacteria could inhibit the growth of their competitors by long distance microbial communication, through the release of metabolites and quorum sensing peptides. This was considered a biological strategy for maintenance of density of commensal species, and elimination of pathogenic bacteria. These functions require a balance in the gut microbiota. Imbalance in the gut microbiota has been linked to several disorders. Polyphenols modulate the gut microbiota. Cocoa is the richest food source of polyphenols on weight basis.

DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC