2.1. The Good

11 to 1012 per milliliter [ Bacteroides and Prevotella ) and Firmicutes ( Lactobacillus , Bacillus , Clostridium , Enterococcus , Staphylococcus , Ruminicoccus , Faecalibacterium , Roseburia , Dialister , and Sphingobacterium ) which constitutes 90% of the gut microbiome, followed by Actinobacteria ( Corynebacterium , Bifidobacterium , and Atopobium ), Proteobacteria ( Escherichia , Shigella , Desulfovibrio , Bilophila , and Helicobacter ), Fusobacteria ( Fusobacterium ), and Verrucomicrobia ( Akkermansia ) [ Salmonella enterica , Campylobacter jejuni , Escherichia coli , Vibrio cholera and Bacteroides fragilis , yet in low proportions [ The human gastrointestinal (GI) tract caters more than 100 trillion micro-organisms [ 23 ] whereas the estimate on the density of bacterial cells in the colon is 10to 10per milliliter [ 24 ]. Under normal physiologic conditions, the gut microbiota exerts many vital functions in human hosts when it comes to the metabolism of nutrients and drugs, maintenance of integrity of the gastrointestinal mucosal barrier, immunomodulatory roles and even protection against exogenous pathogens [ 25 ]. Clinicians and researchers have learned that a healthy and stabilized gut flora becomes largely responsible for regular metabolic functions and thus the overall health condition of human hosts. As a matter of fact, increasing interest indicates that the scientific community is beginning to view the GMB as a sort of “secretory and modulatory” organ. A large scale study previously estimated that the human GMB contains approximately 35,000 bacterial species [ 26 ], but the two major constituent phyla predominating a healthy GMB are Bacteroidetes (and) and Firmicutes (, and) which constitutes 90% of the gut microbiome, followed by Actinobacteria (, and), Proteobacteria (, and), Fusobacteria (), and Verrucomicrobia () [ 24 27 ], which are known to be essential in maintaining a healthy microbe–host relationship [ 25 ]. Despite this major genetic profile, distribution of bacterial species can vary a lot from the beginning of the esophagus all the way down to the distal ends of the GIT. Remarkably, the large intestines contain over 70% of all the microbes found in the human body [ 25 ]. The human colon also provides a suitable home for primary pathogenic species such asand, yet in low proportions [ 28 ]. Currently, it is already well-established that age of the human (fetus, neonate, infant, child, adolescent, adult, or geriatric), GI tract (caecum, colon, rectum), gestational age (preterm or full term birth), type of delivery (natural labor or cesarean section), method of feeding (breast milk, artificial milk, supplementary feeds, or complimentary feeds), dietary habits, and antibiotic administration (clarithromycin, vancomycin, ciprofloxacin, or clindamycin) are notable variables which can transform and affect the GMB environment as a whole [ 27 ]. These transformations, in turn, can be either beneficial or quite detrimental depending on additional intrinsic and extrinsic factors that play out in distinct patterns on a per-patient basis [ 25 ].

For obvious reasons, the innate immune system is programmed to attack several micro-organisms which are not recognized as “self” components of the host. However, the truth is that most of the bacterial populations in the GMB are non-pathogenic. In fact, it is usually quite the opposite; they can co-exist harmoniously with other cells in the host in symbiotic fashion [ 25 ]. The symbiotic relationship of the GMB in the intestines, for instance, is much appreciated not only for the assistance of GMB in nutrient and drug metabolism, but also for their ability to act on the immune system in order to induce protective responses to prevent colonization and invasion by extraneous pathogens via the production of antimicrobial signals and competitive inhibition for nutrient and adhesion sites [ 29 ].

Bacteroides , Roseburia , Bifidobacterium , Fecalibacterium , and Enterobacteria can ferment indigestible oligosaccharides and produce short chain fatty acids (SCFA) including butyrate, propionate, and acetate, which are rich sources of energy for the host in addition to playing vital health roles [ Oxalobacter formigenes , Lactobacillus species , and Bifidobacterium species can process and degrade oxalate in the intestinal tract, reducing risk of urinary tract complications [ Speaking of nutrients, these microbes obtain their nutrients from fermented dietary carbohydrates. Colonic species such as, andcan ferment indigestible oligosaccharides and produce short chain fatty acids (SCFA) including butyrate, propionate, and acetate, which are rich sources of energy for the host in addition to playing vital health roles [ 30 ]. Butyrate, for example, prevents the accumulation of toxic residual products such as D-lactate [ 31 ]. Bacteroides, once again, are of particular research interest due to their renowned expression of glycosyl transferases, glycoside hydrolases and polysaccharide lyases, which are remarkable enzymes involved in carbohydrate metabolism. It turns out that the metabolic pathway involving carbohydrate fermentation also culminates in the synthesis of oxalate; however, additional bacterial organisms such as, andcan process and degrade oxalate in the intestinal tract, reducing risk of urinary tract complications [ 32 33 ].

Bacteroides thetaiotaomicron , for example, can enhance the efficiency of lipid hydrolysis by increasing the expression of certain co-enzymes that work with pancreatic lipase during lipid digestion [ Bacteroides intestinalis , Bacteroides fragilis and E. coli , have demonstrated the ability to deconjugate and dehydrate the primary bile acids, converting them into the secondary bile acids such as deoxycholic and lithocolic acids, assisting in the maintenance of a healthy GI tract [ Moreover, in terms of metabolic syndrome, these microbes also play an essential role in lipid metabolism., for example, can enhance the efficiency of lipid hydrolysis by increasing the expression of certain co-enzymes that work with pancreatic lipase during lipid digestion [ 34 ]. Lipid digestion and energy metabolism is an essential component that must be adequately regulated in order to prevent problems such as dyslipidemia, which is a key risk factor of metabolic syndrome. Elaborating further, members of this particular genus can synthesize conjugated linoleic acid, which is known to promote antidiabetic, hypolipidemic, antiobesogenic, and antiatherogenic effects, therefore being an extremely valuable player in the fight against metabolic abnormalities as a whole [ 35 ].and, have demonstrated the ability to deconjugate and dehydrate the primary bile acids, converting them into the secondary bile acids such as deoxycholic and lithocolic acids, assisting in the maintenance of a healthy GI tract [ 36 ]. The secondary effects generated by gut microbes also allow increases in serum concentrations of metabolites including pyruvic, citric, fumaric and malic acids, which reflect increased energy metabolism [ 37 ].

Protein metabolism in humans is also partially attributed to the GMB due to the secretion of microbial proteinases and peptidases that play a cooperative role with human proteinases [ 25 ]. An example worthy of mention is the amino acid transport that occurs on the bacterial cell wall, in symbiotic fashion. As the amino acids from the intestinal lumen are passed into the bacteria, gene products end up converting these molecules into small signaling molecules and even antimicrobial peptides [ 38 ].

Another important activity is the processing of polyphenols, which humans often obtain from a balanced diet enriched with a variety of plants, fruits, and their associated products. Polyphenolic compounds such as flavanols, flavones, isoflavones, tannins, lignans, chlorogenic acids and anthocyanidins are absorbed in the intestines [ 25 ]. In general, these molecules are kept in their precursor forms as glycosylated derivatives bound to sugars until they reach the GI tract, where they are activated after removal of glycosylated structures by the GMB [ 39 ]. Interestingly, the structural specificity of the polyphenol molecules and the variety and richness in the gut niche strongly dictates the level of the processing capacity in the host’s intestine [ 25 ]. Once activated by the GMB, the activated polyphenols get absorbed by the intestinal circulation and subsequently delivered to distant tissues and organ systems in the body, where they will be able to promote additional healthy roles, such as antimicrobial properties [ 39 ].