Substrate Supply to the Colonic Microbiota
An adult colon contains approximately 500 g of contents, most of which is bacteria , and about 100 g/day is voided as stool. A typical western type diet supplies the colonic microbiota with about 50 g daily of potentially fermentable substrate, predominantly dietary fiber (DF). Non-starch polysaccharides (NSP) are major components of DF and account for 20%–45% of the dry matter supplied to the colon. Simple sugars and oligosaccharides each represent a further 10% whereas starch (and starch hydrolysis products) supplies less than 8% of dry matter. Some sugar alcohols also escape small intestine (SI) absorption and are minor dietary substrates for the colonic microbiota . About 5–15 g of protein and 5–10 g of lipid passes into the proximal colon daily, largely of dietary origin. Various other minor dietary constituents, including polyphenols, catechins, lignin, tannins and micronutrients also nourish colonic microbes. About 90% of the approximately 1 g/day of dietary polyphenols escapes digestion and absorption in the SI [60,61] and can have significant influence on microbial populations and activities [62,63,64].
Carbohydrates—Importance for Large Bowel Fermentation and Health
Carbohydrates are the principal carbon and energy source for colonic microbes. Collectively, they have an immense capacity to hydrolyse a vast range of these nutrients, especially complex polysaccharides .
DF is integral to a healthy diet and Australian adults consume ~27 g each day , which is greater than in other high income countries, including the USA (<20 g/day). Epidemiological and experimental studies show that DF is both preventative and therapeutic for many large bowel disorders and other conditions or diseases, including cardiovascular diseases, type II diabetes and obesity [67,68,69,70,71].
One mechanism by which fiber promotes and maintains bowel health is through increasing digesta mass. Incompletely fermented fiber (e.g., insoluble NSP such as cellulose), increases digesta mass primarily though its physical presence and ability to adsorb water. An increase in digesta mass dilutes toxins, reduces intracolonic pressure, shortens transit time and increases defecation frequency. Fibers can also increase fecal mass to a lesser degree by stimulating fermentation, which leads to bacterial proliferation and increased biomass .
Many of the health benefits ascribed to fiber are a consequence of their fermentation by the colonic microbiota and the metabolites that are produced. Carbohydrates are fermented to organic acids that provide energy for other bacteria, the bowel epithelium and peripheral tissues. SCFA are the major endproducts of carbohydrate fermentation. These weak acids (pKa ~4.8) help lower the pH within the colon thereby inhibiting the growth and activity of pathogenic bacteria. Other minor organic acids produced include lactate, succinate and formate. Branched-chain SCFA (e.g., isobutyrate and isovalerate) results from fermentation of branched chain amino acids .
There are spatial gradients in microorganisms along the length of the gut. Bacterial growth and metabolic activity (fermentation) is greatest in the proximal colon where substrate availability is at a maximum [13,73]. Accordingly, pH progressively increases as stool progresses from the proximal to distal colon (from 5.8 to 7.0–7.5), largely because of the progressive depletion of carbohydrate substrates and absorption of SCFA, and increasing efficiency of protein fermentation and production of alkaline metabolites . Total SCFA concentrations are highest in the proximal colon (~100 mM) and decline progressively toward the distal colon. Acetate, propionate and butyrate are the major individual SCFA, accounting for 90% of the total, with molar ratios approximating 65:20:15 .
Butyrate has attracted significant attention because it serves as the principal source of metabolic energy for the colonocytes , is instrumental in maintaining mucosal integrity, modulates intestinal inflammation and promotes genomic stability. The capacity of butyrate to regulate colonocyte differentiation and apoptosis, promoting removal of dysfunctional cells, underscores its potential to protect against colon cancer .
The SCFA also have roles beyond the gut and may improve risk of metabolic and immune system diseases and disorders, such as osteoarthritis, obesity, type II diabetes and cardiovascular disease [13,76].
More than 90% of the total SCFA produced in the colon is absorbed by the epithelium, through mechanisms that are not fully elucidated. SCFA-stimulated sodium-coupled transport in the apical membrane of colonocytes is especially important as it mediates (co)absorption of water and helps recover electrolytes as well as energy . The SCFA can bind to G-protein coupled receptors in colorectal tissues, particularly GPR 41 and 43, which may influence immune function and tumour suppression, but these pathways are still relatively poorly characterized .
Most of the absorbed acetate reaches the liver via the portal vein, whereas propionate, and butyrate to an even larger extent, is metabolized extensively by colonocytes. Acetate and propionate are used by the liver for oxidation, and for lipogenesis and gluconeogenesis, respectively. Hepatic metabolic clearance of SCFA is very high and so concentrations in the systemic bloodstream are about 100-fold lower than those in colonic digesta and feces (~50 µM versus 100 mM, respectively) .