**5.2. Fiber, carbohydrate metabolism, and diabetes mellitus**

It is known that exists a link among an elevated body mass index, waist circumference and the risk of type 2 diabetes mellitus [54,55]. The role of DF in weight reduction has been examined in animal and human studies. A reduced risk for type 2 diabetes mellitus (T2DM) appears to depend on the type and dose of dietary fiber and the study population [36]. In mice, 10% psyllium and 10% sugar cane fiber decreased the fasting blood glucose and fasting plasma insulin when added to a high fat diet for 12 weeks, compared to the insoluble fiber cellulose [56]. β-Glucan also improved the glucose tolerance and decreased the serum insulin in mice when added to a high fat diet at a 2% and 4% level [57]. In humans, muffins high in β-glucan and resistant starch lowered the postprandial blood glucose and insulin levels [58]**.** A prospective cohort design with 252 women was used to measure energy intake, dietary fat intake, fiber intake, body weight, body fat percentage, physical activity, season of assessment, age and time between assessments. They concluded that increasing dietary fiber intake significantly reduced the risk of gaining weight and fat in women, independent of several potential confounders such as: physical activity, dietary fat intake, and others [59]. Another study about the consumption of soluble viscous fiber, that included one hundred and seventy six men and women, reached the same conclusions [60]. Other biomarkers such as Glycemic Index (GI) and Glycemic Load (GL) when they are high were both associated with an increased risk of diabetes in a meta-analysis of observational studies [61,62]. On the other hand, numerous epidemiological studies performed to date relate to a high intake of dietary fiber with low levels of GI and GL [63-65]. Moreover, DF has also shown to be effective improving altered parameters in obesity and T2DM [66,67]. Soluble viscous fiber plays an important role in controlling satiety and postprandial glycemic and insulin responses [68] and some studies showed that insoluble dietary fiber improved the quality of life for these patients [69]

The protective effect of DF on obesity and T2DM has been historically attributed to greater satiety due to an increased mastication, calorie displacement, and decreased absorption of macronutrients [55]. This mechanism is associated with the ability of soluble fibers to form viscous solutions that prolong gastric emptying, consequently inhibiting the transport of glucose, triglycerides and cholesterol across the intestine [70-72]. Recently, it was observed that both soluble and insoluble DFs also modifies carbohydrate metabolism by influencing the expression of hormones such as glucose-dependent insulin tropic polypeptide and glucagon-like peptide-1, that stimulate postprandial insulin release, enhance glucose tolerance, and delay gastric emptying [73-76].

### **5.3. Fiber and gut microflora**

The large intestine plays host to a large and diverse resident microflora. Over the last 10-15 years, 16S ribosomal RNA analyses has allowed a more complete characterization of the diverse bacterial species that make up this population [77]. Around 95% of human colonic microflora (as estimated from faecal sampling) appear to be within Bacteroides and Clostridium phylogenic groups, with less than 2% of the total microflora being made up of Lactobacilli and bifidobacteria [78]. In general, the colonic microflora is partitioned from the rest of the body by the mucus layer and mucosa. Loss of this partitioning effect is associated with disease processes within the large intestine [79], but it is unsure whether this is a cause or -effect of the disease process. Within the healthy large intestine, the main way the colonic microflora interacts with the host is through its metabolites [80]. Some of these metabolites are putatively damaging to the underlying mucosa, such as indoles, ammonia and amines while others are potentially beneficial to the host, including short chain fatty acids (SCFA) [81] and lignans that the mammalian gut can absorb [82,83]. SCFA are produced by bacterial fermentation of dietary carbohydrate sources, of which dietary fiber is the main type in the large intestinal lumen.

Dietary fiber, plays a profound role on the number and diversity of bacteria that inhabit the large intestine. In the absence of dietary fiber or other luminal energy sources, resident bacteria in the colon will turn to large intestinal mucus as an energy source prior to attacking the underlying mucosa [84]. As bacteria require the necessary enzymes to break down saccharide bonds of the diverse range of dietary fibers, fiber will clearly affect microfloral population dynamics. The presence of any fermentable dietary fiber is likely to lead to an increase in microfloral bifidobacterial and Lactobacillus levels, as these bacteria ferment carbohydrates. Previous studies in humans have suggested dietary fibers like alginate [85], chitosan [86], and inulin [87] lead to a reduction in potentially harmful microfloral metabolites. A range of small human interventions with various fermentable dietary fibers have shown significant, but small, clinical benefit in a number of intestinal diseases and disorders either on their own or in combination with probiotics [88-90].

Catabolism by microbial populations may also be important for decrease the levels of cholesterol and lipids. Bacteria such as Lactobacillus and Bifidobacteria can exert a hypocholesterolemic effect by enhancing bile acid deconjugation [91,92]. Furthermore, Lactobacillus and Bifidobacteria remove cholesterol in vitro by assimilation and precipitation [93,94]. Fermentation products further affect lipid metabolism. Propionate inhibits the incorporation of acetic acid into fats and sterols, resulting in decreased fatty acid and cholesterol synthesis [95].

## **5.4. Fiber and Immune function**

462 The Complex World of Polysaccharides

quality of life for these patients [69]

tolerance, and delay gastric emptying [73-76].

**5.3. Fiber and gut microflora** 

**5.2. Fiber, carbohydrate metabolism, and diabetes mellitus** 

It is known that exists a link among an elevated body mass index, waist circumference and the risk of type 2 diabetes mellitus [54,55]. The role of DF in weight reduction has been examined in animal and human studies. A reduced risk for type 2 diabetes mellitus (T2DM) appears to depend on the type and dose of dietary fiber and the study population [36]. In mice, 10% psyllium and 10% sugar cane fiber decreased the fasting blood glucose and fasting plasma insulin when added to a high fat diet for 12 weeks, compared to the insoluble fiber cellulose [56]. β-Glucan also improved the glucose tolerance and decreased the serum insulin in mice when added to a high fat diet at a 2% and 4% level [57]. In humans, muffins high in β-glucan and resistant starch lowered the postprandial blood glucose and insulin levels [58]**.** A prospective cohort design with 252 women was used to measure energy intake, dietary fat intake, fiber intake, body weight, body fat percentage, physical activity, season of assessment, age and time between assessments. They concluded that increasing dietary fiber intake significantly reduced the risk of gaining weight and fat in women, independent of several potential confounders such as: physical activity, dietary fat intake, and others [59]. Another study about the consumption of soluble viscous fiber, that included one hundred and seventy six men and women, reached the same conclusions [60]. Other biomarkers such as Glycemic Index (GI) and Glycemic Load (GL) when they are high were both associated with an increased risk of diabetes in a meta-analysis of observational studies [61,62]. On the other hand, numerous epidemiological studies performed to date relate to a high intake of dietary fiber with low levels of GI and GL [63-65]. Moreover, DF has also shown to be effective improving altered parameters in obesity and T2DM [66,67]. Soluble viscous fiber plays an important role in controlling satiety and postprandial glycemic and insulin responses [68] and some studies showed that insoluble dietary fiber improved the

The protective effect of DF on obesity and T2DM has been historically attributed to greater satiety due to an increased mastication, calorie displacement, and decreased absorption of macronutrients [55]. This mechanism is associated with the ability of soluble fibers to form viscous solutions that prolong gastric emptying, consequently inhibiting the transport of glucose, triglycerides and cholesterol across the intestine [70-72]. Recently, it was observed that both soluble and insoluble DFs also modifies carbohydrate metabolism by influencing the expression of hormones such as glucose-dependent insulin tropic polypeptide and glucagon-like peptide-1, that stimulate postprandial insulin release, enhance glucose

The large intestine plays host to a large and diverse resident microflora. Over the last 10-15 years, 16S ribosomal RNA analyses has allowed a more complete characterization of the diverse bacterial species that make up this population [77]. Around 95% of human colonic microflora (as estimated from faecal sampling) appear to be within Bacteroides and Clostridium phylogenic groups, with less than 2% of the total microflora being made up of Besides its absorptive functions, the gastrointestinal tract is involved with a range of immune functions. The mucosa effectively partitions the rest of the body from digestive enzymes, large numbers of bacteria and assorted toxins that occur within the gut. The mucosa has two main roles in immunity. Firstly, the mucosa samples luminal contents to assess the threat to the body because the gut comes into contact with a wide range of external antigenic compounds. This is carried out by the gut-associated lymphoid tissue or GALT [96]. In the second place, gut epithelium must also protect itself from the luminal stress of damaging agents and shear forces [97]. To do this, protective mucus is secreted along almost the entirety of the gastrointestinal tract (excluding the oesophagus and possibly Peyer's patches). Within the mouth, mucin is secreted alongside other salivary secretions and acts as a lubricant. In the stomach and intestine, mucus is secreted as a protective barrier [98].

There is a paucity of data regarding intake of DFs and immune function associated with the gut or otherwise in humans [99]. Animal studies within this area are also sparse. Field et al. [100] carried out studies with dogs and they found that fermentable fiber intake resulted in increased intra-epithelial T-cell mitogen response [92]. In a recent study it has been observed that DF may interact directly with immunoregulatory cells. Mucosal macrophages and dendritic cells have receptors with carbohydrate-binding domains that bind β-glucans and cause a decrease in IL-12 and increase in IL-10, which is consistent with an antiinflammatory phenotype [101]. No previous study has assessed the impact of DFs on the human mucus barrier due to the invasiveness of procedures involved with measuring the mucus barrier directly. However, the effects of different types of DFs on the intestinal mucus barrier have been studied in animal models. Fibers and fiber sources such as alginates, ispaghula husk, wheat bran, ulvan and carrageenan all appear to benefit the protective potential of the colonic mucus barrier [100,102].

#### **5.5. Fiber and prevention of cancer**

Cancer continues to be one of the number one health concerns of populations worldwide. Most cancers strike both men and women at about the same rate, with exception of cancers of the reproductive system. Of particular concern is cancer of the colon, ranking among the top 3 forms of cancer in the U.S.A., for both men and women. Colon cancer is also one of the leading causes of cancer morbidity and mortality among both men and women in the Western countries, including the U.S.A. [103]. The European Prospective Investigation of Cancer (EPIC) is a project that includes more than half a million people in 10 European countries and they results indicate that dietary fiber provides strong protective effects against colon and rectal cancer. In one of its papers, the authors clarify that methodological differences in some previous studies (e.g., study design, dietary assessment instruments, definition of fiber) may account for the lack of convincing evidence for the inverse association between fiber intake and colorectal cancer risk [104]. A careful work within the same project was conducted as a prospective case–control study nested within seven UK cohort studies which included 579 patients who developed incident colorectal cancer and 1996 matched control subjects. They used standardized dietary data obtained from 4- to 7 day food diaries that were completed by all participants to calculate the odds ratios for colorectal, colon, and rectal cancers. In this work, the researchers confirmed that the intake of dietary fiber is inversely associated with colorectal cancer risk [105]. Taking into account these studies, the United States Food and Drug Administration has approved health claims in 2010 supporting the role of DF in the prevention of cancer [106].

Human metabolic and animal model studies indicate that beneficial effects of dietary fiber in relation to colon cancer development depend on the composition and physical properties of the fiber [107,108]. The effect of soluble fiber sources is mainly based on their fermentation and on the effects of short-chain fatty acids produced, especially of butyric acid. It has been known since 1982 that the colonic mucosa uses these acids, especially butyrate, as a preferential energy source [109]. Butyric acid stimulates the proliferation of normal cell lines both in vitro and in the normal epithelium, but retards the growth of carcinoma cell lines and induces apoptosis in cultured colonic adenoma and carcinoma cells [110,111]. Insoluble fiber has been found to have a protecting effect by absorbing hydrophobic carcinogens [112-114]. A third potentially effective mechanism is that of the accompanying phenolic compounds. Several phenolic compounds, having antioxidative properties, are present especially in cereal fiber sources. They are released from their bound states by bacterial enzymatic action in the colon, and can act in the intestine locally as anticarcinogens both in preventing cancer initiation and progression [115-117].

464 The Complex World of Polysaccharides

protective potential of the colonic mucus barrier [100,102].

in 2010 supporting the role of DF in the prevention of cancer [106].

**5.5. Fiber and prevention of cancer** 

There is a paucity of data regarding intake of DFs and immune function associated with the gut or otherwise in humans [99]. Animal studies within this area are also sparse. Field et al. [100] carried out studies with dogs and they found that fermentable fiber intake resulted in increased intra-epithelial T-cell mitogen response [92]. In a recent study it has been observed that DF may interact directly with immunoregulatory cells. Mucosal macrophages and dendritic cells have receptors with carbohydrate-binding domains that bind β-glucans and cause a decrease in IL-12 and increase in IL-10, which is consistent with an antiinflammatory phenotype [101]. No previous study has assessed the impact of DFs on the human mucus barrier due to the invasiveness of procedures involved with measuring the mucus barrier directly. However, the effects of different types of DFs on the intestinal mucus barrier have been studied in animal models. Fibers and fiber sources such as alginates, ispaghula husk, wheat bran, ulvan and carrageenan all appear to benefit the

Cancer continues to be one of the number one health concerns of populations worldwide. Most cancers strike both men and women at about the same rate, with exception of cancers of the reproductive system. Of particular concern is cancer of the colon, ranking among the top 3 forms of cancer in the U.S.A., for both men and women. Colon cancer is also one of the leading causes of cancer morbidity and mortality among both men and women in the Western countries, including the U.S.A. [103]. The European Prospective Investigation of Cancer (EPIC) is a project that includes more than half a million people in 10 European countries and they results indicate that dietary fiber provides strong protective effects against colon and rectal cancer. In one of its papers, the authors clarify that methodological differences in some previous studies (e.g., study design, dietary assessment instruments, definition of fiber) may account for the lack of convincing evidence for the inverse association between fiber intake and colorectal cancer risk [104]. A careful work within the same project was conducted as a prospective case–control study nested within seven UK cohort studies which included 579 patients who developed incident colorectal cancer and 1996 matched control subjects. They used standardized dietary data obtained from 4- to 7 day food diaries that were completed by all participants to calculate the odds ratios for colorectal, colon, and rectal cancers. In this work, the researchers confirmed that the intake of dietary fiber is inversely associated with colorectal cancer risk [105]. Taking into account these studies, the United States Food and Drug Administration has approved health claims

Human metabolic and animal model studies indicate that beneficial effects of dietary fiber in relation to colon cancer development depend on the composition and physical properties of the fiber [107,108]. The effect of soluble fiber sources is mainly based on their fermentation and on the effects of short-chain fatty acids produced, especially of butyric acid. It has been known since 1982 that the colonic mucosa uses these acids, especially butyrate, as a preferential energy source [109]. Butyric acid stimulates the proliferation of normal cell lines both in vitro and in the normal epithelium, but retards the growth of
