Introduction
This chapter describes a comparison between our predictive equations developed to estimate FC from dietary records for a secondary analysis of a previous study conducted at the SUERC, which measured urinary excretion of SCFA.
Epidemiological studies have frequently reported that diets rich in NDCs may reduce the risk of chronic diseases including CVD (Crowe et al., 2012), CRC (Aune et al., 2011b, Bingham et al., 2003), diabetes mellitus (Carter et al., 2010) and obesity (Bäckhed et al., 2007). Similar results were also found by the World Cancer Research Fund in their major systematic review, they reported that NDCs ‘‘probably’ protect against CRC incidence when there is a high cereals, fruits and vegetables intake (WCRF, 2007). Cereal fibre was the main component behind these protective effects, as NDCs are mainly found in whole grain cereals, pulses, fruit and vegetables (Guillon and Champ, 2000b). According to the European Food Safety Authority (EFSA) report, the average dietary fibre intake is 15 - 30 g per day with the lowest at 6 - 9 g/d and the highest at 39 - 51 g/d in adults across European countries (Agostoni et al., 2010). Therefore, this amount of variation allowed the differences in intake to be compared to investigate if there are any protective effects.
The main characteristics of NDCs are their relatively high content of RS, NDOs and NSPs; these components were shown in intervention studies to induce and sustain improvements to metabolic syndrome risk factors such as, CVD and diabetes mellitus (Steffen et al., 2003, Maki et al., 2012). Steffen et al. (2003) showed that adolescence who consumed of more than 1½ servings of whole grain foods per day were leaner and more insulin sensitive, when compared to those who consumed less than ½ serving per day. Other research shows a healthy diet supplemented with psyllium fibre at a concentration of 30 g/d improve insulin sensitivity, body weight and BMI, when compared with the control (Pal and Radavelli‐Bagatini, 2012). There are many other studies that show the benefit of NDCs, for example Maki et al. (2012) observed that consumption of 15 - 30 g/d of high-amylose maize resistant starch (HAM-RS2) for 4 weeks, enhanced insulin sensitivity in overweight and obese men. Additionally, Lipoprotein profiles in patients with CVD improved after intake of 10.5 g/d of soluble fibre (psyllium ovata husk) for 8 weeks, more than a comparable amount of those of insoluble fibre (psyllium ovata seeds) (Sola et al., 2007a). Othman et al. (2011) conducted a systematic review to study the relationship
between oat β-glucan consumption and blood cholesterol level reduction. They found that a daily intake of at least 3 g of oat β-glucan may reduce plasma total and LDL cholesterol levels by 5 - 10 % in hypercholesterolemic subjects. In a randomized crossover study conducted by Willis et al. (2009) the results showed that 8 g of RS intake kept subjects significantly less hungry than the baseline reading for 120 minutes, and satisfied for the180 minute test period. This effect was also observed by Cani et al. (2006) who found that consumption of either 8 g of oligofructose or dextrin maltose twice a day for two weeks at breakfast, significantly reduced total energy 5 % per day and increased satiety. It is likely that the effects of NSP, NDOs and RS observed in these studies are brought about through the fermentation of NDCs in the colon, which results in the production of the SCFAs (Kimura et al., 2014).
The principal components of SCFAs are the end products of luminal microbial fermentation of predominantly NDCs (den Besten et al., 2013). SCFAs are produced in varying amounts depending on the diet and the composition of the intestinal microbiota, with different carbon chain lengths (acetate (C2), propionate (C3), butyrate (C4), valerate (C5) and caproate (C6)) creating different end products (van Nuenen et al., 2003). Several studies have shown that SCFAs not only exert effects in the colonic epithelial cells, but also enter the circulation and have an impact on metabolic processes in other tissues and organs, for example acetate and propionate have been shown to have an impact on glucose and lipid metabolism in the liver (Chen et al., 1984, Wolever et al., 1989, Venter et al., 1990a, Nishina and Freedland, 1990). Acetate is used in the liver as substrate for the synthesis of cholesterol and fatty acids, whereas it appears propionate inhibits these processes (Nishina and Freedland, 1990). The deorphanization of the free fatty acid (FFA) receptors FFA2 (GPR43) and FFA3 (GPR41) are activated by SCFAs and this effect of SCFA is likely to occur in adipose tissue metabolism due to the high expression of GPR43 in these tissues (Hong et al., 2005). Ge et al. (2008) observed that the anti-lipolytic effect is abolished in adipocytes isolated from GPR43 knockout animals, and this suggests there is a potential role for acetate and propionate in regulating plasma lipid profiles through activation of GPR43. In addition, some studies have suggested that FFA2 might play a role in regulation of appetite and metabolism (Sleeth et al., 2010, Psaltopoulou et al., 2010).
There is evidence to suggest a high fibre diet is associated with weight reduction and a lower incidence of diabetes (Psaltopoulou et al., 2010). Several studies have shown that SCFAs produced by colonic fermentation of fibre may be responsible for this through FFA2 activation (Sleeth et al., 2010, Zhou et al., 2008). Moreover, a high fibre diet has been linked with increased levels of PYY, a hormone known to decrease appetite (Karra and Batterham, 2010). Karaki et al. (2008) observed that FFA2 is responsible for PYY secretion in entero-endocrine L-cells and these L-cells are also responsible for GLP-1 secretion, an effective anorectic incretin hormone, which also regulates insulin secretion from pancreatic β-cells and can increase insulin sensitivity in target tissues (Tolhurst et al., 2012). Further evidence for the importance of these cells comes from the work by Tolhurst et al. (2012) who confirmed that FFA2 and FFA3 expression are enriched in L-cells, and FFA2 mediate SCFAs promoted GLP-1 discharge from mixed colonic cultures in vitro. These findings suggest that the FFA2 receptor might have potential to be used as a therapeutic for treatment of type 2 diabetes and related metabolic conditions.
Studies have shown that butyrate provides 70 % of the energy required by the colonocytes for cellular respiration, it influences a wide range of cellular functions affecting colonic health; it may also have an anti-carcinogenic and anti-inflammatory potential, and can affect the intestinal barrier and play a role in satiety (Hamer et al., 2008). Further evidence for its anti-cancer properties comes from studies that have reported that Butyrate has a protective effect against colon cancer and adenoma development (Bornet et al., 2002). Several studies have reported that butyrate inhibits proliferation, induces differentiation and apoptosis in CRC cells in vitro, at concentrations similar to those found in the large bowel in vivo (Fung et al., 2012, Thangaraju et al., 2009). Other studies have shown that high butyrate production reduces the incidence of carcinogen-induced colon tumours in rodent models, partly through induction of apoptosis (Clarke et al., 2008, Le Leu et al., 2009).
The primary mechanisms of butyrate anti-inflammatory action are through the suppression of nuclear factor κB (NFkB) activation, the inhibition of interferon γ production, the upregulation of peroxisome proliferator-activated receptor γ (PPARγ), and possibly through the inhibition of histone deacetylase (HDAC) (Hamer et al., 2008).
The effect of NDCs has been further investigated in intervention studies, for example in ulcerative colitis (UC) patients, which proposed that high intake of NDCs stimulate luminal butyrate production, and may results in an improvement of the inflammation and symptoms (Hallert et al., 2003, Vernia et al., 2003). The study involved twenty two quiescent UC patients being advised to add 20 g of NDCs to their daily diet, and the results showed a significant increase of faecal butyrate concentration, and improvement of abdominal symptoms, after four weeks of NDCs intake (Hallert et al., 2003). In a double-blind, placebo-controlled multicenter trial, Vernia et al. (2003) observed that patients with active distal UC who were treated with rectal enemas containing 5-ASA plus sodium butyrate (80 mM) twice a day, show a significant improvement of the disease activity score, compared with those treated with 5- aminosalicylic acid (5-ASA) alone. These studies suggest butyrate is a useful therapy for the treatment of this condition.
Studies have shown that butyrate and propionate favorably activate FFAR3 more than acetate, which leads to suppressing weight gain and stimulating gut hormones (Gao et al., 2009, Lin et al., 2012). This has been further studied by Lin et al. (2012) who fed FFAR3 knockout mice and wild-type littermates with standard chow diet, and for one week with high fat diet (HFD). They observed that the FFAR3 knockout mice showed no significant difference in body weight compared to their wild-type littermates on standard chow and HFD diets. Then the HFD was supplemented with butyrate and propionate and provided to the mice for eight days. The results showed that the butyrate and propionate inhibited weight gain and food intake in FFAR3 knockouts to the same extent as in wild-type mice. Moreover, Gao et al. (2009) reported that a HFD supplemented with butyrate (5 % wt/wt) reduced obesity and insulin resistance in obese mice; they also observed that the plasma butyrate concentration increased and blood lipids decreased, showing that butyrate has an effect on lipid profiles as well as suppressing weight gain. The results of these studies showed that butyrate and propionate have an impact on reducing body weight and lipids profiles.
Numerous studies have shown that urinary output can be used as functional markers of human vitamin C status for individual and population dietary intake assessments (Carr et al., 2012, Carr et al., 2013). In randomized cross-over study of fifteen male university students for 4 weeks, Carr et al. (2012) examined the effect of a high vitamin C containing fruit intake such as kiwifruit on blood plasma and urine
vitamin C levels and specifically to determine the dosage required to reach ‘healthy’ and ‘optimal’ levels. They observed that one kiwifruit per day was sufficient to achieve ‘healthy’ plasma and urine levels of vitamin C (>50 µmol/l) and with 2 or 3 per day, ‘optimal’ plasma and urine levels of the vitamin were reached. They have suggested that plasma and urinary vitamin C may reflects dietary intake. On the other hand, most of interventional studies in this area have demonstrated that consumption of diets rich in NDCs, such as cereals, fruit and vegetables might be protective against CVD, CRC, obesity, satiety and diabetes, and it is believed that some of the protective effects of NDCs may be attributed to their fermentation to SCFA in the colon by the colonic microbiota (Tan et al., 2013). However, until now these interventional studies have relied on many food composition tables’ old values, due to the lack of new values (Westenbrink et al., 2013b). Additionally, the amount of NDCs that enters the colon is difficult to estimate because we cannot measure SCFA production, not all non-digestible fibres are fully fermented, and some dietary components normally considered to be fully digested and absorbed in the small intestine may actually escape and enter the colon, for example fructose if eaten in large amounts (Cummings, 1997). RS intake is difficult to determine because any handling of starchy foods in the diet, for example mixing with water, heating, homogenization, freezing or cooling, may affect RS content (Sharma et al., 2008). Overall the importance of FC on colonic health remains unrecognized, mainly because there is no validated method to study SCFA production and colonic fermentation in vivo, the only way to quantify NDC intake is food tables; however, most FC may be hidden in food tables, not defined or unavailable (Westenbrink et al., 2013b). Therefore, an index of FC value needs to be developed to determine the bioactive fraction and to predict SCFA production in the colon.
This chapter describes the further development of the equations to predict FC in the diet, based on the content of NDCs in foods, their fermentability and an approximation of RS content. This was then compared with urinary SCFA concentrations measured in human volunteers who had kept 7 day dietary diaries.
Objectives
The objectives of the study were:
1. To develop an index to estimate FC in the diet from dietary records to predict SCFA production in the colon in vivo in humans
2. Assessment of the relationship between FC intake and urinary excretion of SCFA products for human volunteers based on their habitual diet