Update on the gut microbiome in health and diseases

Table 1 Definitions related to gut microbiome and its action

Terminology	Significance
Microbiota	All microorganisms living in the gut
Microbioma	Sum of microbes, their genetic information, and their ecological niche
Metagenome	Total genes providing information on genetic potential
Indigenous microbiota	Resident gut microbiota in the healthy subjects
Dysbiosis	Modification of the composition of gut microbiota causing diseases
Pathobionts	Gut microbiota causing diseases

Table 2 Distribution of normal gut flora in different parts of intestine

Intestine sections	Function	Normal flora
Stomach	Acid production, pepsin, amylase, CFU < 103/mL	Lactobacillus; Streptococcus; Helicobacter pylori
Small intestine: Duodenum, jejunum	Pancreatic enzymes, bicarbonate ions, bile salts, CFU: 103-104/mL	Lactobacilli; Enterococci, Streptococci; Actinobacteria
Small intestine: Ileum	CFU: 103-109/mL	Enterococcus; Bacteroidetes; Lactobacillus; Clostridium; Corynebacteria
Large intestine: Cecum, colon	Mucus and bicarbonate; CFU: 1010-1012/mL	Bacteroidetes; Clostridium; Eubacterium; Ruminococcus; Streptococcus; Enterococcus; Lactobacillus; Fusobacteria

CFU: Colony-forming unit.

Table 3 Metabolites produced by gut microbiota and their functions

Metabolites	Functions	Ref.
Bile acid metabolites; including deoxycholic acid and lithocholic acid	Regulate bile acid, cholesterol, lipid, glucose, and activate host nuclear receptors and cell signaling pathways	Ramírez-Macías et al[39]
Short-chain fatty acids metabolites	Regulate food intake and insulin secretion, also aid in maintaining body weight	Psichas et al[40]
Branched-chain fatty acids including isobutyrate	Histone deacetylase inhibition, increased histone acetylation	Mischke et al[41]
Indole derivatives including indoxyl sulfate and IPA	IPA exhibits neuroprotective effects, acts as a powerful antioxidant and regulates intestinal barrier function	Hendrikx et al[42]
Lipopolysaccharide, peptidoglycan, lipoteicholic acid	Epigenetic regulation of genes in colorectal cancer, modulation of chromatine structure and transcriptional activity	Lightfoot et al[43]
Phenolic derivatives include 4-OH phenylacetic acid, urolithins, enterodiol and 9-prenylaringenin	Exhibit antimicrobial effect, maintain intestinal health and protect against oxidative stress	Larrosa et al[44]
Choline metabolites include choline, trimethylamine N-oxide, and betaine	Regulating lipid metabolism, and glucose synthesis contribute to the development of cardiovascular disease	Smallwood et al[45]
Polyamines include putrescine, spermidine and spermine	Sustaining the high proliferation rate of intestinal epithelial cells enhances intestinal barrier integrity and enhances the systematic adaptive immune system	Rooks et al[46]
Vitamins including thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6) panthotenic acid (B5), biotin (B7), folate (B11, B9), cobalamin (B12), and menaquinone (K2)	Help in red blood cell formation, DNA replication, and repair, work as an enzymatic co-factor, and enhance immune functioning	Nicholson et al[47]
Ethanol	Protein fermentation metabolism may be involved in NAFLD progression	Yao et al[48]
Hydrogen sulfide	Reduction/neutralization of reactive oxygen species	Afanas'ev et al[49]

IPA: Indole-3-propionic acid; NAFLD: Non-alcoholic fatty liver disease.

Table 4 Examples of gut microbiota-derived metabolites and their beneficial effects on human health

Metabolite	Pathway	Microbial agent	Health benefits
Butyrate	Carbohydrate metabolism	Clostridia; Faecalibacterium prausnitzii; Coprococcus catus; Anaerostipes hadrus	Increased intestinal barrier function; Modulate intestinal macrophage function; Suppression of colonic inflammation; Improvements in insulin sensitivity
Propionate	Carbohydrate metabolism	Blautia obeum; Coprococcus catus; Roseburia inulinivorans; Prevotella copri	Suppression of colonic inflammation; Decreased innate immune response to microbial stimulation; Protection from allergic airway inflammation; Improvements in insulin sensitivity and weight control in obese mice
Indole	Tryptophan metabolism	Lactobacillus; Bifinobacterium longum; Bacteroides fragilis	Maintenance of host-microbe homeostasis at mucosal surfaces via IL-22; Increased barrier function; Modulation of host metabolism
Indole-3-aldehyde	Tryptophan metabolism	Lactobacillus	Maintenance of mucosal homeostasis and intestinal barrier function via increased IL-22 production; Protection against intestinal inflammation in mouse models of colitis
Indole-3-propionate	Tryptophan metabolism	Clostridium sporogenes	Maintenance of intestinal barrier function and mucosal homeostasis; Increased production of antioxidant and neuroprotectant products
10-hydroxy-cis-12-octadecoate	Linoleic acid derivative (lipid metabolism)	Lactobacillus	Maintenance of intestinal barrier function; Decreased inflammation; Increased intestinal IgA production

IgA: Immunoglobulin A; IL-22: Interleukin 22.

Table 5 Some examples of potentially harmful gut microbiota bacterial species

Bacteria	Associated physiologic changes	Associated diseases states
Bacteroides	Activate CD4+ T cells	Increased with animal-based diet; Increased in obesity
Bilophila	Promote pro-inflammatory immunity	Increased in colitis; Decreased in autism
Clostridium	Promote generation Th17 cells	Increased after smoke exposure; Increased in autism and Rett syndrome; Positive correlation with plasma insulin and weight gain; Increased in type 2 diabetes; Clostridium perfrigens increased in old age
Escherichia coli	TLR activation	Increased in inflammatory bowel disease; Increased in type 2 diabetes
Neisseria	Sugar fermentation	Only two species are pathogenic: Neisseria meningitides and Neisseria gonorrhoeae

Th17: T helper 17: TLR: Toll-like receptor.

Table 6 Diseases associated with gut microbiota abnormalities

Disease	Features
Irritable bowel syndrome	An abundance of Firmicutes and a decrease of Bacteroidetes
Type I diabetes	In genetically predisposed individuals, autoimmune against pancreatic β-cells. Deficient development or alteration of the microbiota may contribute to dysfunctional immunity with the devastation of autoimmune β-cells and increased leakiness of the intestinal barrier. Variability of microbiomes reduced
Asthma	Outbreaks of Chlamidophila pneumonia during bronchitis and pneumonia development affect the airway microbiome. Gut microbiota is influenced by the introduction of microbiota to the environment, particularly in early life, which helps immune function growth and the development of defending against allergic sensitization
Food-borne pathogens and food poisoning	Opportunistic pathogens (Campylobacter, Salmonella, Escherichia coli, Shigella) disturb the microbiome’s balance leading to dysbiosis
Malnutrition	Decrease or missing species that either process food categories efficiently or produce vitamins may reduce the absorption of nutrients. An overabundance of Enetrobacteriaceae can lead to epithelial damage, diarrhea, and limited absorption of nutrients
Depression	In physiologic system, Bifidobacterium infantis, generally found in infants’ gastrointestinal tract and administered probiotic drugs, can have antidepressant effects
Anxiety	Oral administration of Campylobacter jejuni subclinical doses in murine models induced anxiety like behavior without stimulating immunity