Here we present the recent research that supports the contention that replacement of rapidly digested carbohydrates with carbohydrates resistant to digestion (fibers and prebiotics) may counteract obesity and prevent many non-communicable diseases (1) (2) (3) (4) (5).  If one accepts the premise that hyperglycemia and hyperinsulinemia from high glycemic carbohydrates (HGC)  are  amongst the most important causes of obesity and accelerated aging (6) (7) (8) (9) (10), finding a suitable replacement for HGC becomes a dilemma as they form the bulk of ingredients stocked in our supermarkets and convenience stores.  There is a limited availability of alternatives to HGC and replacement with protein (11) is problematic and too much fat adds to calorie concerns, but fiber is chronically deficient from modern diets and it was a much larger part of the diet of our evolutionary ancestors when metabolic adaptations to plant foods became established over tens of millions of years (12).

Carbohydrates that are not digested or slowly digested can be broadly classified as fiber which provides a substrate for fermentation by symbiotic intestinal micro-organisms, this so called prebiotic effect is now subject of intense medical research.  Grazing animals eat little other than fiber and they obtain nutrition from products of fermentation by symbiotic microorganisms that produce large amounts of short chain fatty acids which provide their main energy source.  SCFA’s have important cell signaling effects and serve as an energy substrate in man as well as other mammals.  Besides SCFA there are many other beneficial products of bacterial fermentation as the levels of essential vitamins, such as folate and biotin, may be higher in individuals than their diet would suggest. This can be attributed to microbial production of folate and biotin, as well as a number of vitamins, including other water soluble B vitamins and vitamin K. It was assumed that, as these vitamins were produced in the colon, they would not be absorbed, but excreted. This notion was challenged with the discovery of colonic transporters for biotin, thiamine, riboflavin, pyridoxine and folate (13).

There have been numerous epidemiological studies and controlled trials on fiber consumption which have prompted the European and American food safety authorities to approve several health claims associated with increased fiber consumption:

• In epidemiological studies fiber has been shown to decrease the risk of diabetes, cardio-vascular disease, and Obesity (14) (13) (15) (16) (17)
• The European Food Safety Authority and the FDA have approved health claims related to several sources of fiber that improve intestinal function, reduce cholesterol levels and reduce the risk of cardio-vascular disease.
• Barley fiber was shown to reduce hypothalamic hormones of appetite and energy regulation (18).
• Cholesterol and bile salt Excretion: Fiber assists the excretory function of the liver and enhances intestinal transit time resulting in improved lipid profiles with high fiber diets (12) (19).
• Plant foods with high fiber content are filling relative to calorie content and limit the amount of calories that can be comfortably consumed (2) (20).
• Fiber, Fecal Bulk and Intestinal Motility:  Fiber has a high oil binding capacity and can absorb 5 to 10 times its volume of fats and cholesterol.  Faecal loss of calories is frequently underestimated particularly so with increased faecal output from high fiber consumption (21).  Calorie content of faeces is around 2 Cals per gm (22) and the typical low fiber Western Diet (10-15 gms/d) might be associated with a faecal output of 100 g/day and this could rise to 200-400 g/d with recommended (35 g/d) or even higher fiber intakes (21) which may result in faecal calorie output of between 400 and 800 Cals/day.  Studies have indicated a 1 g/d increase in fiber results in a 5 gm/d increase in stool weight but of that the calorie content, particularly from fat, increases proportionately more (23).

The molecular mechanisms behind numerous beneficial effects of fiber are being resolved by basic science researchers (24).  Acetate, propionate and butyrate are the most common SCFA’s produced by bacterial fermentation of fiber which takes place mainly in the terminal ileum and large intestine.  The SCFA’s, particularly butyrate, are important energy substrates for intestinal epithelial cells and excess SCFA passes through to the liver and systemic circulation performing dual roles as an energy substrate and cell signaling.  Two G-protein coupled receptors for SCFA have been identified FFAR2 and FFAR3 which preferentially bind acetate/propionate and butyrate respectively (25).  There is a direct link between fiber consumption producing SCFA and increased GLP1 secretion from intestinal L cells which is triggered via the SCFA receptors FFAR2 and 3.  In addition SCFA’s can have direct effects on gene expression by inhibition of Histone Deacetylases HDAC(26) which has anti-proliferative and anti-inflammatory effects in vitro, and in in vivo models of intestinal inflammation (27) and either of these mechanisms are thought to be responsible for widespread beneficial effects of SCFA as listed below:

• SCFA reduce inflammation and regulate adipokine secretion in adipose tissue (14) increasing leptin and decreasing the pro-inflammatory resistin.
• SCFA has anti-inflammatory effects in colitis, arthritis and asthma (28)
• SCFA induce T regulatory cells important in controlling intestinal barrier functions and immunity (26)
• Acetate modulates mitochondrial function through PPARs, PGC1alpha, SIRT1 and SIRT3 with possible effects on aging (29)
• SCFA trigger Glucagon Like Peptide release from intestinal L cells (30). GLP1 slows gastric emptying, lowers glucose levels, and reduces food consumption.  GLP1 is an important regulator of glucose metabolism and also suppresses appetite (30).
• GLP1 has been recently shown to stimulate apolipoprotein A-I gene expression in hepatocytes in culture (31) with important implications for increasing plasma HDL and protection against cardiovascular disease.
• GLP1 prevents the accumulation of monocytes and macrophages in arterial wall and suppresses proinflammatory cytokine expression in macrophages (32).
• SCFA stimulate secretion of anorexic hormone PYY from intestinal L cells (30).
• SCFA also inhibit the secretion of the orexigenic hormone ghrelin (33).
• SCFA reduce endothelial cell expression of leukocyte adhesion molecules VCAM and ICAM which are important in the development of cardio-vascular diseases (34)
• Short chain fatty acid products of fiber fermentation are important energy sources.  Colonic epithelial cells may be dependent of SCFA’s as they become stressed and undergo apoptosis in the absence of butyrate (35) (13).

Summary

Protective effects of fiber consumption are well documented in empirical studies and are now being backed up with plausible molecular mechanisms.  Short chain fatty acid products of intestinal fermentation of fiber activate specific receptors that are widely expressed throughout body tissue importantly on immune cells and adipose tissue and suppress inflammation while the FFAR2 receptors in intestinal cells produce additional signaling molecules GLP1 and PYY which suppress appetite, stimulate hepatic HDL production and contribute to further anti-inflammatory and metabolic regulatory functions.  In view of the mounting evidence fiber deficiency is a serious problem of modern dietary culture as suggested by Surgeon Captain Peter Cleave in 1974 way back before the obesity epidemic began.

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