**Abstract**

The gut microbiome consists of bacteria, protozoans, viruses, and archaea collectively called as gut microbiota. Gut microbiome (GM) modulates a variety of physiological responses ranging from immune and inflammatory responses, neuronal signalling, gut barrier integrity and mobility, synthesis of vitamins, steroid hormones, neurotransmitters to metabolism of branched-chain aromatic amino acids, bile salts, and drugs. Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder that is featured by imbalance in blood glucose level, altered lipid profile, and their deleterious consequences. GM dysbiosis a major factor behind the incidence and progression of insulin resistance and is responsible for altering of intestinal barrier functions, host metabolic, and signaling pathways. The GM of type 2 diabetes (T2DM) patients is characterized by reduced levels of Firmicutes and Clostridia and an increased ratio of Bacteroidetes:Firmicutes. Endotoxemia stimulates a low-grade inflammatory response, which is known to trigger T2DM. Xenobiotics including dietary components, antibiotics, and nonsteroidal antiinflammatory drugs strongly affect the gut microbial composition and can promote dysbiosis. However, the exact mechanisms behind the dynamics of gut microbes and their impact on host metabolism are yet to be deciphered. Interventions that can restore equilibrium in the GM have beneficial effects and can improve glycemic control.

**Keywords:** type 2 diabetes, inflammation, immune response, gut microbiome, xenobiotics

## **1. Introduction**

Our quality of life and health status are modulated by our food habits and lifestyle. Hence several metabolic disorders and are the greatest global health issues are influenced by improper diet and lifestyle [1]. The other factors that are involved in the development of metabolic disorders and diseases are environmental factors, maternal health, and host genetic makeup. The resident microorganisms in our gastrointestinal tract are collectively collected as the gut microbiota (GM). GM consists of bacteria, fungi, Archaea, protozoa, and viruses. In case of mammals, GM comprises of four main phyla: Firmicutes (64%), Bacteroidetes (23%), Proteobacteria (8%), and Actinobacteria (3%). These phyla are important for the

regulation of host metabolism and physiology [2]. The total number of both prokaryotic cells and host eukaryotic cells in the gut is approximately 100 trillion, which is three times that of the total number of human body cells [3]. Hence, our unique gut environment is considered as a functional and measurable organ [4]. However, the composition of GM varies along the gastrointestinal tract, and differs within and between individuals depending on the gestational age, mode of delivery, breastfeeding, antibiotic exposure, dietary lifestyle and nutritional status of the individual status of [5, 6]. The colonization of GM is limited in stomach and small intestine, but quite dense and diverse in the colon owing to the absence of digestive secretions, slow peristalsis, and rich nutrient supply [7]. This variety in composition of GM and its function is influenced by the consumption of improper diet, which in turn affects the health condition of the host. GM regulates the energy homeostasis, intestinal integrity and immunity against invading pathogens by participating in the digestive process and energy production, hampering pathogen colonization, and modulating the immune system; hence GM can modulate the overall health status of the host. Gut microbiome also influences an individual's metabolic status such as calorie derived from indigestible dietary substances and storage of calories in adipose tissue, which regulates incidence of obesity in an individual. Studies from germ-free and wild type mice showed alteration in homeostasis in kidney, liver, and intestine in germ-free mice depicting the fact that GM influences whole body metabolism [8–13]. GM also plays a vital role in vitamin production, energy harvest and storage, fermentation and absorption of undigested carbohydrates. The distribution of GM is determined by diet to a large extent as evident from individuals who follow a diet high in animal fat have dominance of Bacteroides in GM, whereas those who follow a carbohydrate-rich diet have a *Prevotella* dominant GM (**Table 1**) [14–16]. According to conventional theories the relationship between genetic and environmental factors such as high-calorie diet and lack of physical activities was considered as the major main contributor to obesity but recently GM has attracted much attention in relation to human health and disease. Recent scientific investigations have shown that GM can be considered as an important endogenous factor controlling obesity [17, 18].

## **2. Host-gut microbiota metabolite interaction**

Several reports have shown that the metabolites derived by GM from fermentation of food play a key role in maintenance of the host metabolism. Clostridium and Eubacterium from our GM break down bile acid in the intestine to its secondary metabolites like deoxycholic acid and lithocholic acid. These metabolites bind to Takeda G protein coupled receptor-5 TGR5 receptor (G-protein-coupled bile receptor) present in the endocrine glands, adipocytes, muscles, immune organs, spinal cord and enteric nervous system, and stimulates the secretion of incretin hormone GLP-1 and insulin. Hence these metabolites in turn promote energy expenditure (**Table 1**) [19]. Long chain fatty acids, for example linoleic acid produced by the GM regulates our lipid profile finally resulting in obesity [20]. Short chain fatty acids (SCFs) another secondary metabolite of gut microbial fermentation is formed by the digestion of indigestible polysaccharides and oligosaccharides that are neither digested nor absorbed in the proximal jejunum [21]. SCFs mainly acetate and propionate contributed by Bacteroidetes and butyrate produced by Firmicutes balance the host metabolism by influencing energy homeostasis, lipid accumulation and appetite [22]. SCF produced in the gastrointestinal tract are also known to control the pH of the lumen by increasing the absorption of nutrients. SCFs also act as a source of nutrition for GM due to high carbon content [23]. Butyrate is the main source of energy for colonocytes. It aids in the proliferation, maturation,

**157**

*An Insight into the Changing Scenario of Gut Microbiome during Type 2 Diabetes*

Bifidobacteria Population reduces in high fat-fed mice gut increasing endotoxemia [14] Bacteroidetes Population high in the gut of people consuming animal-based food rich diet [15] *Prevotella* Population high in the gut of people consuming plant-based food rich diet [16] *Clostridium* and *Eubacterium* Break down bile acid in the intestine to its secondary metabolites

hormone GLP-1 and insulin [19]

plasma and diminishes endotoxemia [63]

hyperinsulinemic rats induced by high-fructose [65]

Low population in GM of T2DM patients [113]

90% of the bacterial species present in gut [15, 16]

Metformin increases the populations of *Akkermansia* sp. in high-fat diet-fed mice, hence improving glucose metabolism. Oral administration of *Akkermansia muciniphila* also improves metabolic dysfunctions like endotoxemia and adipose tissue inflammation [122]

probiotics control GM through CB2 receptor expression [76]

bacteremia in early stages of T2D [64]

*Lactobacillus reuteri* GMNL-263 They are capable of reducing T2D markers like serum glucose,

*Lactobacillus casei* Shirota They can increase lipopolysaccharide-binding protein expression in

*Bifidobacterium animalis* subsp. lactis They can restrict bacterial translocation in intestine alleviating

*L. casei* Zhang Oral administration can ameliorate impaired glucose tolerance in

*Lactobacillus* Oral administration is positively correlated with expression of CB2 receptor [76] *Clostridium* Oral administration is negatively correlated with CB2 expression

*Bifidobacterium infantis* Impairs inflammation by altering the intestinal permeability [80, 81]

High in T2D patients [113, 121]

Bacteroidetes:Firmicutes ratio Low in GM of obese patients [112, 113]

Enterobacteriaceae Population elevated by T2D drugs [122] *Clostridium* and *Eubacterium* Population lowered by T2D drugs [122]

Butyrate-producing bacteria (*Roseburia* species and *Faecalibacterium prausnitzii*)

*Facts and effects of various types of bacteria present in GM*

Firmicutes (Gram-positive) and Bacteroidetes (Gram-negative)

Proteobacteria and particularly

*Escherichia coli*

*Akkermansia* sp. *Akkermansia muciniphila*

**Table 1.**

like deoxycholic acid and lithocholic acid. These metabolites bind to TGR5 receptor (G-protein-coupled receptor) present in the endocrine glands, adipocytes, muscles, immune organs, spinal cord and enteric nervous system, and stimulates the secretion of incretin

glycated hemoglobin and c-peptide in high-fructose-fed rats along with reduction in inflammatory cytokines IL-6 and TNF-α in adipose tissue and down-regulated forms of GLUT 4 and PPAR-γ [58]

maintenance of colonocytes and also protects the colon by enhancing mucin expression and immune response [24]. Acetate and propionate can cross the liver epithelium, and propionate gets metabolized in the liver, whereas acetate stays in the peripheral circulation [25]. SCF also regulates epithelial barrier integrity by maintaining the tight junction proteins like claudin-1, occludin, and Zonula Occludens-1. Suppression of these proteins leads to invasion of bacteria and lipopolysaccharides (LPS) stimulating an inflammatory response [26]. Hence SCF acts as energy source and also regulates host biological responses including inflammation, oxidative

*DOI: http://dx.doi.org/10.5772/intechopen.90697*

**Gut microbiota Facts and effects**


*An Insight into the Changing Scenario of Gut Microbiome during Type 2 Diabetes DOI: http://dx.doi.org/10.5772/intechopen.90697*

#### **Table 1.**

*Parasitology and Microbiology Research*

**2. Host-gut microbiota metabolite interaction**

Several reports have shown that the metabolites derived by GM from fermentation of food play a key role in maintenance of the host metabolism. Clostridium and Eubacterium from our GM break down bile acid in the intestine to its secondary metabolites like deoxycholic acid and lithocholic acid. These metabolites bind to Takeda G protein coupled receptor-5 TGR5 receptor (G-protein-coupled bile receptor) present in the endocrine glands, adipocytes, muscles, immune organs, spinal cord and enteric nervous system, and stimulates the secretion of incretin hormone GLP-1 and insulin. Hence these metabolites in turn promote energy expenditure (**Table 1**) [19]. Long chain fatty acids, for example linoleic acid produced by the GM regulates our lipid profile finally resulting in obesity [20]. Short chain fatty acids (SCFs) another secondary metabolite of gut microbial fermentation is formed by the digestion of indigestible polysaccharides and oligosaccharides that are neither digested nor absorbed in the proximal jejunum [21]. SCFs mainly acetate and propionate contributed by Bacteroidetes and butyrate produced by Firmicutes balance the host metabolism by influencing energy homeostasis, lipid accumulation and appetite [22]. SCF produced in the gastrointestinal tract are also known to control the pH of the lumen by increasing the absorption of nutrients. SCFs also act as a source of nutrition for GM due to high carbon content [23]. Butyrate is the main source of energy for colonocytes. It aids in the proliferation, maturation,

regulation of host metabolism and physiology [2]. The total number of both prokaryotic cells and host eukaryotic cells in the gut is approximately 100 trillion, which is three times that of the total number of human body cells [3]. Hence, our unique gut environment is considered as a functional and measurable organ [4]. However, the composition of GM varies along the gastrointestinal tract, and differs within and between individuals depending on the gestational age, mode of delivery, breastfeeding, antibiotic exposure, dietary lifestyle and nutritional status of the individual status of [5, 6]. The colonization of GM is limited in stomach and small intestine, but quite dense and diverse in the colon owing to the absence of digestive secretions, slow peristalsis, and rich nutrient supply [7]. This variety in composition of GM and its function is influenced by the consumption of improper diet, which in turn affects the health condition of the host. GM regulates the energy homeostasis, intestinal integrity and immunity against invading pathogens by participating in the digestive process and energy production, hampering pathogen colonization, and modulating the immune system; hence GM can modulate the overall health status of the host. Gut microbiome also influences an individual's metabolic status such as calorie derived from indigestible dietary substances and storage of calories in adipose tissue, which regulates incidence of obesity in an individual. Studies from germ-free and wild type mice showed alteration in homeostasis in kidney, liver, and intestine in germ-free mice depicting the fact that GM influences whole body metabolism [8–13]. GM also plays a vital role in vitamin production, energy harvest and storage, fermentation and absorption of undigested carbohydrates. The distribution of GM is determined by diet to a large extent as evident from individuals who follow a diet high in animal fat have dominance of Bacteroides in GM, whereas those who follow a carbohydrate-rich diet have a *Prevotella* dominant GM (**Table 1**) [14–16]. According to conventional theories the relationship between genetic and environmental factors such as high-calorie diet and lack of physical activities was considered as the major main contributor to obesity but recently GM has attracted much attention in relation to human health and disease. Recent scientific investigations have shown that GM can be considered as an important endogenous factor controlling obesity [17, 18].

**156**

*Facts and effects of various types of bacteria present in GM*

maintenance of colonocytes and also protects the colon by enhancing mucin expression and immune response [24]. Acetate and propionate can cross the liver epithelium, and propionate gets metabolized in the liver, whereas acetate stays in the peripheral circulation [25]. SCF also regulates epithelial barrier integrity by maintaining the tight junction proteins like claudin-1, occludin, and Zonula Occludens-1. Suppression of these proteins leads to invasion of bacteria and lipopolysaccharides (LPS) stimulating an inflammatory response [26]. Hence SCF acts as energy source and also regulates host biological responses including inflammation, oxidative

stress, and immune response toward Crohn's disease, ulcerative colitis, and colorectal cancer [27, 28]. Host metabolism is activated by SCFs by direct stimulation of G-coupled receptors like free fatty acid receptors 2 and 3 (FFAR2/GPR41 and FFAR3/GPR41) occurring mainly in the gut epithelial cells. They also activate host metabolism by inhibiting nuclear class I histone deacetylases (HDACs) present in the epithelial cells [27]. FFAR2 acts as the receptor for acetate and FFAR3 is the receptor for butyrate and propionate. Activation of these receptors regulates the level of satiety hormones like ghrelin (orexigenic peptide), glucagon like peptide-1 (GLP-1), and peptide YY (PYY) (anorexigenic peptide) [29]. Ghrelin secretion occurs pre-meal, while GLP-1 and PYY are secreted post-meal, which in turn stimulates insulin production in the pancreatic cells. GLP-1 and PYY also reduce food intake, normalizes weight loss and maintain the balance of energy intake. Increase in the production of SCFs enhances the secretion of PYY and GLP-1 but decreases secretion of ghrelin, which ultimately leads to increased satiety and reduction in food intake [30]. The other factors inducing reduced appetite is mediated by butyrate and propionate by (i) enhanced expression of leptin in adipocytes, direct regulation of body weight and energy homeostasis by decreased food intake and upregulated energy expenditure [31], (ii) promoting gluconeogenesis in the intestinal cells [32] and (iii) inhibition of histone acetyltransferase and deacetylases which exhibit anti-inflammatory responses, epigenetic modification necessary for proliferation and differentiation of immune cells, activated AMP-activated protein kinase (AMPK) pathway synchronised adiponectin secretion, induction of mitochondrial biogenesis and fatty acid oxidation [33]. In healthy subjects SCF regulates integrity of gut, secretion of hormones, and immune responses, while in metabolically unhealthy subjects SCF implements protection from diabetes, ulcerative colitis, colorectal cancer, and neurodegenerative disorders [24, 34].

## **2.1 Gut microbiota composition**

Recent studies targeting metagenomics have disclosed that approximately 90% of the bacterial species in the GM of adult humans are Bacteroidetes (Gramnegative) and Firmicutes (Gram-positive) [35, 36]. A healthy person fosters 500–1000 bacterial species at a single time and almost 1012–1014 colony-forming units (CFU) with a total mass weight of about 1–2 kg in the total gut [37] with 109–1012 CFU/ml in the colon, 101–103 CFU/ml in jejunum and 104–108 CFU/ml in the ileum [38]. Transfer of microbiota from mother to embryo takes place in utero or during birth and attains strength by the 2 years. Composition of GM is shaped by host genetics, environmental factors and early exposure to microbes during birth. The other factors that regulate formation of a stale GM are exposure to vaginal microbiome during normal delivery, skin microbiota during cesarean sections, breast-feeding and antibiotics in neonatal or early childhood.

#### **2.2 Role of gut microbiota in carbohydrate metabolism**

Normal diet of a healthy human contains a considerable percentage of carbohydrates comprising of monosaccharides, disaccharides and complex polysaccharides. The difference lies in the absorption of the sugars, for example common sugars like cane sugar and fruit sugars are readily absorbed in the intestine, disaccharides like maltose, lactose and sucrose and complex polysaccharides like pectin, starch and hemicellulose are broken down into monosaccharides in the ileum with the help of bacterial enzymes like glycosidases before being absorbed [39]. After food intake consisting of carbohydrate-rich diet, glucose levels in the blood rise, and later are strongly regulated and kept at a homeostatic level by the help of two hormones,

**159**

enterocytes.

**2.4 Role of probiotics upon gut microbiota**

*An Insight into the Changing Scenario of Gut Microbiome during Type 2 Diabetes*

insulin and glucagon. Carbohydrate digestion and absorption occurs in the upper digestive tract via glucose transporters called GLUTs (glucose transporters) located on the epithelial cells [40]. GLUT proteins uptake glucose into the pancreatic β-cells. Metabolization of glucose stimulates insulin secretion due to increased ATP/ ADP ratio, membrane depolarization and closure of potassium channels, resulting

The role of gut environment and gut associated lymphoid tissue plays a pivotal

In the earlier sections it has been discusses that our GM plays a key role in digestion and absorption of food. Increased population of Bacteroidetes lead to increase in energy production. The population of Bifidobacteria reduce in high fat-fed mice gut increasing endotoxemia. Prebiotic supplementation can restore Bifidobacteria levels in the mouse gut [48, 49]. Bacteroidetes are more widespread in the gut of people consuming animal-based food rich diet. *Prevotella* is prevalent in people consuming plant-based food rich diet. In case of people consuming plant-based foods, the GM produce more SCFAs and increased synthesis of amylase, glutamate and riboflavin [50, 51]. On the contrary, people consuming animal-based foods have GM modified for increased catabolic processes as for example degradation of glycans and amino acids [52]. SCFAs like butyrate, propionate and acetate along with some gases like hydrogen are produced by the breakdown of these polysaccharides, are further used in colonic fermentation and yield energy [53]. Butyrates can decrease calorie intake of an individual by inducing satiety via production of GLP-1 and gastric inhibitory peptide-1 [54]. Butyrates are also involved in maintenance of gut integrity by supplying energy for regulating the survival and proliferation of

Low-grade inflammation is a key pathophysiological factor behind the progression of type 2 diabetes (T2D), and incidence of hyperglycemia and insulin resistance [55]. Progression of T2D occurs along with reduced GM diversity and increased gut inflammation. Gut inflammation includes innate immune responses via toll-like receptors, (TLRs) secretion of proinflammatory cytokines and increased endotoxemia. Also during high-fat diet induced obesity, intestinal Gram-negative bacteria translocates in the circulatory system, adipose tissue and cause endotoxemia [56].

Probiotics enhance production of interleukin-10 (IL-10) an important regulatory and anti-inflammatory cytokine in diabetic mice. Increased IL-10 downregulates proinflammatory cytokines like interferon-γ (IFN-γ) and interleukin-2 (IL-2)/interleukin 1-β (IL-1β) preventing inflammation and incidence of diabetes [56, 57]. *Lactobacillus reuteri* GMNL-263 reduces T2D markers like serum glucose, glycated hemoglobin and c-peptide in high-fructose-fed rats along with reduction

role in T2D [42]. T2D is a chronic metabolic disorder characterized by fasting serum hyperglycemia, non-responsiveness of insulin and insulin insufficiency [43]. Insulin resistance or non-responsiveness occurs in the liver and skeletal muscle cells when they undergo failure to sense insulin. Other factors in T2D are non-responsiveness or deficiency of incretins, amplified lipid catabolism, increased glucagon levels in circulation and increased salt and water renal retention [43, 44]. High-fatdiet-fed germ-free mice, wild type mice and standard diet fed mice exhibit different metabolic and immunological characters depending on diet and GM [45, 46]. Also mice belonging to same genotype and diet exhibit different metabolism of glucose

*DOI: http://dx.doi.org/10.5772/intechopen.90697*

in calcium dependant exocytosis of insulin [41].

**2.3 Role of gut microbiota and its association with diet**

depending on their GM [47].

#### *An Insight into the Changing Scenario of Gut Microbiome during Type 2 Diabetes DOI: http://dx.doi.org/10.5772/intechopen.90697*

insulin and glucagon. Carbohydrate digestion and absorption occurs in the upper digestive tract via glucose transporters called GLUTs (glucose transporters) located on the epithelial cells [40]. GLUT proteins uptake glucose into the pancreatic β-cells. Metabolization of glucose stimulates insulin secretion due to increased ATP/ ADP ratio, membrane depolarization and closure of potassium channels, resulting in calcium dependant exocytosis of insulin [41].

The role of gut environment and gut associated lymphoid tissue plays a pivotal role in T2D [42]. T2D is a chronic metabolic disorder characterized by fasting serum hyperglycemia, non-responsiveness of insulin and insulin insufficiency [43]. Insulin resistance or non-responsiveness occurs in the liver and skeletal muscle cells when they undergo failure to sense insulin. Other factors in T2D are non-responsiveness or deficiency of incretins, amplified lipid catabolism, increased glucagon levels in circulation and increased salt and water renal retention [43, 44]. High-fatdiet-fed germ-free mice, wild type mice and standard diet fed mice exhibit different metabolic and immunological characters depending on diet and GM [45, 46]. Also mice belonging to same genotype and diet exhibit different metabolism of glucose depending on their GM [47].

### **2.3 Role of gut microbiota and its association with diet**

In the earlier sections it has been discusses that our GM plays a key role in digestion and absorption of food. Increased population of Bacteroidetes lead to increase in energy production. The population of Bifidobacteria reduce in high fat-fed mice gut increasing endotoxemia. Prebiotic supplementation can restore Bifidobacteria levels in the mouse gut [48, 49]. Bacteroidetes are more widespread in the gut of people consuming animal-based food rich diet. *Prevotella* is prevalent in people consuming plant-based food rich diet. In case of people consuming plant-based foods, the GM produce more SCFAs and increased synthesis of amylase, glutamate and riboflavin [50, 51]. On the contrary, people consuming animal-based foods have GM modified for increased catabolic processes as for example degradation of glycans and amino acids [52]. SCFAs like butyrate, propionate and acetate along with some gases like hydrogen are produced by the breakdown of these polysaccharides, are further used in colonic fermentation and yield energy [53]. Butyrates can decrease calorie intake of an individual by inducing satiety via production of GLP-1 and gastric inhibitory peptide-1 [54]. Butyrates are also involved in maintenance of gut integrity by supplying energy for regulating the survival and proliferation of enterocytes.

Low-grade inflammation is a key pathophysiological factor behind the progression of type 2 diabetes (T2D), and incidence of hyperglycemia and insulin resistance [55]. Progression of T2D occurs along with reduced GM diversity and increased gut inflammation. Gut inflammation includes innate immune responses via toll-like receptors, (TLRs) secretion of proinflammatory cytokines and increased endotoxemia. Also during high-fat diet induced obesity, intestinal Gram-negative bacteria translocates in the circulatory system, adipose tissue and cause endotoxemia [56].

#### **2.4 Role of probiotics upon gut microbiota**

Probiotics enhance production of interleukin-10 (IL-10) an important regulatory and anti-inflammatory cytokine in diabetic mice. Increased IL-10 downregulates proinflammatory cytokines like interferon-γ (IFN-γ) and interleukin-2 (IL-2)/interleukin 1-β (IL-1β) preventing inflammation and incidence of diabetes [56, 57]. *Lactobacillus reuteri* GMNL-263 reduces T2D markers like serum glucose, glycated hemoglobin and c-peptide in high-fructose-fed rats along with reduction

*Parasitology and Microbiology Research*

stress, and immune response toward Crohn's disease, ulcerative colitis, and colorectal cancer [27, 28]. Host metabolism is activated by SCFs by direct stimulation of G-coupled receptors like free fatty acid receptors 2 and 3 (FFAR2/GPR41 and FFAR3/GPR41) occurring mainly in the gut epithelial cells. They also activate host metabolism by inhibiting nuclear class I histone deacetylases (HDACs) present in the epithelial cells [27]. FFAR2 acts as the receptor for acetate and FFAR3 is the receptor for butyrate and propionate. Activation of these receptors regulates the level of satiety hormones like ghrelin (orexigenic peptide), glucagon like peptide-1 (GLP-1), and peptide YY (PYY) (anorexigenic peptide) [29]. Ghrelin secretion occurs pre-meal, while GLP-1 and PYY are secreted post-meal, which in turn stimulates insulin production in the pancreatic cells. GLP-1 and PYY also reduce food intake, normalizes weight loss and maintain the balance of energy intake. Increase in the production of SCFs enhances the secretion of PYY and GLP-1 but decreases secretion of ghrelin, which ultimately leads to increased satiety and reduction in food intake [30]. The other factors inducing reduced appetite is mediated by butyrate and propionate by (i) enhanced expression of leptin in adipocytes, direct regulation of body weight and energy homeostasis by decreased food intake and upregulated energy expenditure [31], (ii) promoting gluconeogenesis in the intestinal cells [32] and (iii) inhibition of histone acetyltransferase and deacetylases which exhibit anti-inflammatory responses, epigenetic modification necessary for proliferation and differentiation of immune cells, activated AMP-activated protein kinase (AMPK) pathway synchronised adiponectin secretion, induction of mitochondrial biogenesis and fatty acid oxidation [33]. In healthy subjects SCF regulates integrity of gut, secretion of hormones, and immune responses, while in metabolically unhealthy subjects SCF implements protection from diabetes, ulcerative colitis,

colorectal cancer, and neurodegenerative disorders [24, 34].

breast-feeding and antibiotics in neonatal or early childhood.

**2.2 Role of gut microbiota in carbohydrate metabolism**

Recent studies targeting metagenomics have disclosed that approximately 90% of the bacterial species in the GM of adult humans are Bacteroidetes (Gramnegative) and Firmicutes (Gram-positive) [35, 36]. A healthy person fosters 500–1000 bacterial species at a single time and almost 1012–1014 colony-forming units (CFU) with a total mass weight of about 1–2 kg in the total gut [37] with 109–1012 CFU/ml in the colon, 101–103 CFU/ml in jejunum and 104–108 CFU/ml in the ileum [38]. Transfer of microbiota from mother to embryo takes place in utero or during birth and attains strength by the 2 years. Composition of GM is shaped by host genetics, environmental factors and early exposure to microbes during birth. The other factors that regulate formation of a stale GM are exposure to vaginal microbiome during normal delivery, skin microbiota during cesarean sections,

Normal diet of a healthy human contains a considerable percentage of carbohydrates comprising of monosaccharides, disaccharides and complex polysaccharides. The difference lies in the absorption of the sugars, for example common sugars like cane sugar and fruit sugars are readily absorbed in the intestine, disaccharides like maltose, lactose and sucrose and complex polysaccharides like pectin, starch and hemicellulose are broken down into monosaccharides in the ileum with the help of bacterial enzymes like glycosidases before being absorbed [39]. After food intake consisting of carbohydrate-rich diet, glucose levels in the blood rise, and later are strongly regulated and kept at a homeostatic level by the help of two hormones,

**2.1 Gut microbiota composition**

**158**

in inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adipose tissue and down-regulated forms of GLUT 4 and peroxisome proliferator activated receptor-γ (PPAR-γ) (**Figure 1** and **Table 1**) [58]. Methodical consumption of probiotic yoghurt reduces inflammatory markers such as highsensitivity C-reactive protein levels in pregnant women and T2D [59, 60]. Probiotic strains decrease oxidative stress in pancreatic tissue, reducing inflammation and apoptosis of pancreatic cells [61]. Probiotic strains also lessen LDL cholesterol and total cholesterol in serum by regulating lipid metabolism, reducing the risk of T2D [62]. Consumption of *Lactobacillus casei* Shirota increase lipopolysaccharidebinding protein expression in plasma and diminishing endotoxemia (**Table 1**) [63]. *Bifidobacterium animalis* sub sp. lactis can restrict bacterial translocation in intestine alleviating bacteremia in early stages of T2D (**Table 1**) [64]. Oral administration of *L. casei* can also ameliorate impaired glucose tolerance in hyperinsulinemic rats induced by high-fructose (**Table 1**) [65].
