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Signaling Pathways Associated with Metabolites of Dietary Fibers Link to Host Health

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Kavita Rani, Jitendra Kumar, Sonia Sangwan, Nampher Masharing, Murli Dhar Mitra and H.B. Singh

Submitted: June 27th, 2021 Reviewed: July 21st, 2021 Published: September 24th, 2021

DOI: 10.5772/intechopen.99586

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Food is a basic requirement for human life and well-being. On the other hand, diet is necessary for growth, health and defense, as well as regulating and assisting the symbiotic gut microbial communities that inhabit in the digestive tract, referred to as the gut microbiota. Diet influences the composition of the gut microbiota. The quality and quantity of diet affects their metabolism which creates a link between diet. The microorganisms in response to the type and amount of dietary intake. Dietary fibers, which includes non-digestible carbohydrates (NDCs) are neither neither-digested nor absorbed and are subjected to bacterial fermentation in the gastrointestinal tract resulting in the formation of different metabolites called SCFAs. The SCFAs have been reported to effect metabolic activities at the molecularlevel. Acetate affects the metabolic pathway through the G-protein-coupled receptor (GPCR) and free fatty acid receptor2 (FFAR2/GPR43) while butyrate and propionate transactivate the peroxisome proliferator-activated receptors (PPARγ/NR1C3) and regulate the PPARγ target gene Angptl4 in colonic cells of the gut. The NDCs via gut microbiota dependent pathway regulate glucose homeostasis, gut integrity and hormone by GPCR, NF-kB, and AMPK-dependent processes. In this chapter, we will focus on dietary fibers, which interact directly with gut microbes and lead to the production of metabolites and discuss how dietary fiber impacts gut microbiota ecology, host physiology, and health and molecule mechanism of dietary fiber on signaling pathway that linked to the host health.


  • dietary fibe
  • gut microbiota ecology
  • host health
  • signaling pathway
  • molecule mechanism

1. Introduction

The human gut harbors a plethora of a complex community of micro-organisms that are vital for host development and physiology. This community of microbes inhabiting the gut called “gut microbiota” represents a mutualistic symbiotic relationship with the host [1]. The host creates a stable environment for the microbes while the microbes offer the host with an array of functions such as digestion of complex dietary macronutrients, minerals and vitamins production, pathogen protection, and immune system maintenance. Studies have shown that the gut microbiota comprises of about 3.8 × 1013 microorganisms [2] belonging to a wide spectrum of about 160 recognized gut bacterial species [3]. Generally, the opus of the gut microbiota is observed to be comparable in all healthy individuals, however the presence of different microbial species is determined by an individual’s dietary habits, dietary patterns and lifestyle [4]. Dietary fibers (DFs) are vital modulators of the gut microbiota composition which directly impacts individual biological processes and homeostasis via the metabolites, a consequent of microbial fermentation of nutrients such as, short-chain unsaturated fats (SCFAs) [5]. The gut microbiota plays a key and essential role in the metabolization of DFs including non-digestible carbohydrates (NDCs), proteins and peptides, which has escape digestion by host enzymes in the upper gut and absorption in the lower digestive tract. These dietary constituents, are then subjected to fermentation by the microbiota in the cecum and colon (Macfarlane and Macfarlane, 2012) resulting in the production different metabolites called SCFAs varying in carbon number which includes mainly acetate (60%), propionate (25%) butyrate (15%) and methane (CH4), carbon dioxide (CO2) gases [6] which are known to have beneficial effects by behaving as signaling molecules via different pathways. From among the different SCFAs produced Acetate is the most abundant and it is used by many gut commensals to produce propionate and butyrate in a growth-promoting cross-feeding process. Moreover, the SCFA, have been shown a to regulate metabolic activities. Acetate affects the metabolic pathway through the G protein-coupled receptor (GPCR) and free fatty acid receptor 2 (FFAR2/GPR43) while butyrate and propionate transactivate the peroxisome proliferator-activated receptorsγ (PPARγ/NR1C3) and regulates the PPARγ target gene Angptl4 in colonic cells of the gut. The FFAR2 signaling pathway regulates the insulin-stimulated lipid accumulation in adipocytes and inflammation however peptide tyrosine-tyrosine and glucagon-like peptide 1 regulate appetite. The NDCs via microbiota dependent pathway regulate glucose homeostasis, gut integrity, and hormone by GPCR, NF-kB, and AMPK-dependent processes. Hence in this chapter, emphasis is given to address the effects of dietary fibers metabolites as prime signaling molecules, through different signaling pathways and their link between gut microbiota and the host health.


2. Dietary fibers (DFs), gut microbiota and SCFAs metabolites

2.1 Dietary fibers (DFs)

Dietary fibles defined by codex alimentarius commission (2009) are edible carbohydrate polymers with varying monomeric units that are impervious to the host digestive enzymes and thus has escape absorption in the small intestines. These includes, (1) edible naturally occurring carbohydrate polymers present in foods such as fruits, vegetables, legumes, and cereals (2) edible carbohydrate polymers obtained from food raw materials by physical, enzymatic, and chemical means and (3) synthetic carbohydrate polymers. In addition, DFs are further divided either into polysaccharides (non-starchpolysaccharides [NSPs], resistant starch [RS], and resistant oligosaccharides [ROs]) or into insoluble and soluble forms [7]. Soluble fibers are fermented by the gut bacteria giving rise to metabolites such as short-chain fatty acids (SCFAs), insoluble forms of fibers such as cellulose and hemi-cellulose may or slowly digested by the gut bacteria and contributes to a fecal bulking effect, as they reach the colon. Delay absorption of glucose and lipids influencing post-prandial metabolism on the other hand are caused by most soluble NSPs, especially polymers with high molecular weight such as guar gum, certain pectins, b-glucans, and psyllium, are viscous, meaning that they are able to form a gel structure in the intestinal tract that can [7]. Food sources such as legumes, vegetables, nuts, seeds, fruits, and cereals forms the sources of soluble and insoluble fibers whereas RS can only be found in starchy foods such as legumes, tubers, cereals, and fruitlike green bananas, whereas pectin’s are more abundant in fruits and some vegetables, whereas b-glucans are found in cereals [8]. Recently, due to low consumption of DFs in the Industrialized Western world Fortification of foods with extracted or synthesized non-digestible carbohydrates is carried out as a strategy to increase fiber intake. Besides, a wide range of commercial DFs are currently available [9] worldwide, called “prebiotics” on the fact that they exert health benefits by selectively inducing beneficial bacterial populations in the gut. However, contrastingly, studies have reported that irrespective of the types of fibers, virtually all fibers will induce specific shifts in microbiota composition as a result of competitive interactions, and which of these compositional shifts may be beneficial for health, has not yet been established [10]. Furthermore, the mechanisms that have been established to be beneficial to health, is not calculative on the selective utilization of the carbohydrates but on an integrative effect of bacterial fermentation, producing metabolic compounds (e.g., SCFAs) [11], physiological changes (pH lowering), or protection of the mucus layer [12, 13]. Hence, a change in the emphasis of the prebiotic concept away from the selective effect of specific dietary components on gut microbial communities towards the effects of ecological and functional consequences of fiber fermentation, is more significant for host physiology and health [10].

2.2 Gut microbiota

Microorganisms including several species of bacteria, yeast, and viruses make up the Gut microbiota. Out of the different Bacterial phyla, a few phyla represented, by about 160 species [14] composed the gut microbiota. Some of the dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with phyla Firmicutes and phyla Bacteroidetes [15] making up to 90% of gut microbiota. Clostridium, Enterococcus, Lactobacillus, Bacillus, and Ruminicoccus are among the more than 200 genera in the Firmicutes phylum. Clostridium genera represent 95% of the Firmicutes phyla. Phylum Bacteroidetes consists of Bacteroides and Prevotella as predominant genera. The Actinobacteria a less abundant phylumis mainly represented by the Bifidobacterium genus [15]. Besides, the gut microbiome is to a very large extent affected by dietary administration of fiber, which alters the gut microbiota by providing substrates for microbial growth, and expansion of their populations [7]. The possession of different enzymes, about 130 glycoside hydrolase, 22 polysaccharidelyase, and 16 carbohydrate esterase enzyme families, allows the gut microbiome to switch between different energy sources of fibers depending on their availability [16]. Bacteria such as Firmicutes and Actinobacteria has been found to be prime species, which initiates the degradation of complex substrates [7]. Species such as Bifidobacteriumadolescentis, Ruminoccocusbromii, Eubacteriumrectale, and Parabacteroides distasonisplay significant roles in degrading resistant Starch [1, 17]. The consumption of galactooligosaccharides mainly induces Bifidobacterium species possessing the enzymatic machinery to utilize the substrate [18]. Reports have also suggested that, degradation of complex substates, occurs in a cascade where, different species will contribute equally at different stages towards production of metabolites [7]. Primary fiber degraders are species that initiate the utilization of a complex fiber through what can be considered a “guild” of species [19] or a keystone species. Although R. bromii does not make butyrate, it is considered a keystone species for the breakdown of RS and contributes significantly to butyrate generation in the colon. Other dietary fiber types are expected to have similar keystone species, although they have yet to be discovered.

2.3 SCFAs metabolites

Dietary fibers, are metabolized by the microbiota in the cecum and colon [20] resulting in the formation of major products such as particular, acetate, propionate, and butyrate [21]. However, studies have reported that, microbes can utilize amino acids from dietary proteins and triglycerols from fats [22, 23] to facilitate diminished supply of dietary fermentable fibers resulting in reduced fermentative activity and formation of SCFAs as minor end products [24]. Although, protein fermentation was observed to the SCFA pool but, however dietary proteins mostly give rise to branched-chain fatty acids such asisobutyrate, 2-methylbutyrate, and isovalerate, [25] which are may have a concerning effect as a result of insulin resistance [26].

Acetate (C2) is a major SCFA metabolite produced from pyruvate. Many gut bacteria produce Acetate from pyruvate via acetyl-CoA or the Wood-Ljungdahl pathway, which produces acetate via two branches: (1) the C1-body branch (also known as the Eastern branch) via CO2 reduction to formate and (2) the carbon monoxide branch (also known as the Western branch) via CO2 reduction to CO, which is then combined with a methyl group. Propionate is created when succinate is converted to methylmalonyl-CoA through the succinate pathway. Furthermore, propionate, can also be synthesized from acrylate using lactate as a precursor via the acrylate pathway [27] and via the propanediol pathway using deoxyhexose sugars as substrates [28]. Butyrate, the third main SCFA, is produced by the condensation of two molecules of acetyl-CoA and subsequent reduction to butyryl-CoA, which can then be converted to butyrate by phosphotrans butyrylase and butyrate kinase via the classical pathway [29]. The butyryl-CoA: acetate CoA-transferase enzyme can also convert butyryl-CoA to butyrate [30]. Besides, reports have also shown that some microbes can use both lactate and acetate to synthesize butyrate. Butyrate can also be produced from proteins via the lysine pathway, according to a recent analysis of metagenome data [31], implying that microorganisms in the gut can adjust to dietary changes in order to sustain the synthesis of important metabolites like SCFAs. SCFA levels vary along the length of the gut, with the highest concentrations in the cecum and proximal colon and decreasing towards the distal colon [21].


3. Dietary fibers metabolites signaling mechanism and their health implications

3.1 Molecular mechanism of dietary fibers (DFs) and its metabolites

The metabolites of dietary fibers (DFs) are SCFAs that play a significant role in metabolic diseases prevention and treatment along with some contradictory research finding [32]. The SCFAs formate, lactate, acetate, propionate, and butyrate are produces by the saccharolytic fermentation of the dietary fibrous [33] which have a significant role in the maintenance of health by reducing the chances of development of different disease.

World Health Organization have recommended daily intake of dietary fiber 20 g per 1000 kcal consumed for adults human being and this (20 g per 1000 kcal) quantity of dietary fiber is full filled by the daily consumption 400 g per day of fresh vegetables, fruits and grains ( Modern life style, dietary pattern, seasonality, stress, habitat, consumption of antibiotics and disease cause a drastic change in dietary pattern of individual’s finally leads to gut microbial alteration [34] that influence production of SCAFs. The various physiological functions in the gut (including adding the energy to colonocytes, maintaining their mobility, blood flow, and regularize the movements of electrolytes and nutrients within the lumen) activate and modulate by SCAFs [35]. Colonic cell proliferation, differentiation and integrity mentioned by butyrate along with the major and preferred metabolic substrate for colonocytes 60–70% energy requirement [36]. Propionate maintains glucose homeostasis by gluconeogenic pathway [37]. The expression of leptin has enhanced by propionate and acetate. Leptin is a potent anorectic hormone, in adipocytes [38]. Acetate is a lipogenic SCFAs, reduced levels of acetate would result in decreased lipogenesis [37]. In the rat hepatocytes, acetate act as de novo lipogenesis and cholesterol synthesis, and these two pathways are to be inhibited by propionate [39]. The increased levels of propionate SCFAs would assist in the inhibition of acetate conversion into lipid in adipose tissue and the liver. The DFs via gut microbiota increase the rate of acetate synthesis while reducing the level of propionate in cells [40]. Acetate SCFAs is inversely related to plasma insulin levels [41] and acetate also activates leptin secretion in murine adipocytes [42].

High-fat diet-fed rats have increased acetate (C2) production due to gut microbiota that leads to ghrelin secretion and glucose-stimulated insulin secretion by activation of the parasympathetic nervous system (PNS), apart from these high calorically dense diet through gut microbiota-brain-β-cell axis promotes obesity and health complications by regimenting glucose and lipids homeostasis [43].

New study finding by many researchers groups have suggested that [44, 45] the loss of gut microbiota species from the colonic microbiota is associated to consumption of the high-fat, low-dietary fiber diets and other nutrient intake and diversity of gut microbiome [46, 47]. The fermentable dietary fibers directly govern the diversity of the gut microbiota [48], SCFAs regulate the different physiological activity of host. The majority of SCFAs transported across the mucosa by active transport, mediated by two receptors. The monocarboxylate transporter 1 (MCT-1) and the sodium-coupled monocarboxylate transporter 1 (SMCT-1) receptors. Direct inhibition of histone deacetylases HDACs to directly regulate gene expression and SCFA also effects signaling through G-protein-coupled receptors (GPCRs), this may influence host physiology by modulate biological responses of the host.

3.2 SCFAs sensing signaling pathway

All physiological activities occurring in the body are gut metabolites driven and SCFAs are connecting the link between the gut immunity with microbiota. The crucial role of SCFA has been signified in shaping and regulating both local and peripheral immune systems that respond to host metabolism via inflammatory pathways. Therefore, SCFAs modulate functions of the different systems including the enteric, nervous, endocrine, and blood vascular system serving as a key factor to regulate metabolic disorders and immunity. The dietary fibers metabolites exerted effects via their receptors, like the G protein-coupled receptor (FFAR3/GPR41 and FFAR2/GPR43 and GPR109a) through the inhibition of histone deacetylases and the activation of G-protein coupled receptors [32, 49].

3.3 SCFAs sensing signaling pathway in immunological responses

Gut bacteria produced SCFAs from indigestible saccharides diet precursors and SCFAs transported across the mucosa by active transport mediated by two receptors, monocarboxylate transporter 1 (MCT-1) and sodium-coupled monocarboxylate transporter 1 (SMCT-1) receptors which influence host physiological functions and modulate biological responses of the host. The main mechanism is direct inhibition of histone deacetylases (HDACs) to directly regulate gene expression. HDACs remove acetyl groups (deacetylation) from lysine residues of histones [50]. Transcription of genes is enhanced through inhibition of HDACs function by increasing histone acetylation. Dietary fibers SCFAs inhibit HDACs activity and therefore suppress expression of gene in different cells. Butyrate (C4) SCFAs is the most potent inhibitor of HDACs activity and induces gene activation by facilitating the access of transcription factors to promoter region, such kind’s activity of C4 known as an epigenetic modification of chromatins [51]. The SCFAs-mediated HDACs inhibition, acts as an anti-inflammatory immune response mediated by less production of inflammatory cytokines IL-8, IL-6, and TNFα [52]. Apart from these butyrate and propionate reduced NF-kB activity and inflammatory cytokines [53], showing that the anti-inflammatory effects of SCFAs are mediated through the modulation of NF-kB signaling pathway. Beside this the SCFAs also affect signaling through GPCRs. The SCFAs activate different GPCRs e.g. propionate (C3) is a most potent activator of GPR43. The expression of GPR43 has been reported in the entire gastrointestinal tract (GIT) along with cells of the immune and nervous systems. In GIT, GPR43 is highly expressed in endocrine L-cells of the ileum and colon of intestinal PYY and GLP-1 [54] producing cells as well as on colonocytes and enterocytes. The order of potency was reported as like propionate >butyrate>acetate for GPR41 receptor [55]. The SCFAs control the body weight through the release of leptin in adipose tissue by the expression of GPR41 [56]. The SCFAs play crucial role in metabolic functions of hepatic cells through the FFAR3 signaling pathway without influencing the intestinal environment [57]. Niacin receptor 1 (GPR109a) is activated by C4 at low concentration while highly expressed in adipocytes with a lesser extent is also expressed on immune cells. Activation of GPR109a in adipocytes suppresses lipolysis and the lowering of plasma-free fatty acid levels (FFAs) [58]. Through epigenetic mechanisms via histone acetylation acetate also increases fatty acid synthesis [59]. Therefore these finding could helpful to promote the development of functional foods using SCFAs or dietary significance of non-digestible carbohydrates fiber.

3.4 SCFAs sensing signaling pathway in hormone regulation

Gut microbes regulates the host metabolism by secretion of gut hormone. Gut microbiota induced signal to nearby intestinal enteroendocrine cells through microbial metabolites of DFs. These enteroendocrine cells release metabolically active hormones like GLP-1, PYY, GIP, 5-HT, and CCK which influence feeding behavior, glucose metabolism, insulin sensitivity and adiposity. Dietary components also impact on the composition of gut microbiota which may have further downstream consequences on gut hormone secretion and host metabolism. Enterochromaffin cells (EC) of the gut are the main source of serotonin (5-HT, 5-hydroxytryptamine). The EC is dispersed throughout the GI tract of the host and constitutes about half of all enteroendocrine cells. The gut microbiota influences 5-HT levels in the host. The antibiotic-treated mice study showed that significantly lower levels of EC cell-derived 5-HT when compared to antibiotic free animals. The EC cells can sense microbial metabolites by FFAR2 and FFAR3 signaling mechanisms [60]. PYY (Peptide tyrosine-tyrosine) regulates food intake and satiety through activation of central G protein-coupled Y2 receptors on neuropeptide Y (NPY) and AgRP neurons in arcuate nucleus of hypothalamic part of brain [61]. This is the relay of signaling cascade where by appetite-stimulating NPY neurons are suppressed that allowing for the activation of the satiety-inducing a-MSH / pro-opiomelanocortin (POMC) pathway [62]. The ability of gut microbiota to influence PYY secretion, therefore, gut microbiota has significant implications for the development of metabolic disease and obesity. Study reported that oral administration of C4 increased circulating PYY level [63] by FFAR2/3 signaling. Glucagon-like peptide 1 (GLP-1) augments insulin and inhibits glucagon secretion from the pancreas cells. GLP-1 inhibits gastric emptying and influences satiety and food intake [64, 65]. Orally administrated sodium butyrate in mice has been shown to transiently increase GIP and GLP-1 secretion and GIP level were associated with adiposity reported the ileal infusion of acetate, propionate, and butyrate during feeding in pigs, increased plasma CCK levels and paradoxically inhibit pancreatic secretion [66]. SCFAs are influence insulin function via their receptors [67, 68]. Glucose homeostasis in type 2 diabetes mellitus patients managed by fiber reaches diet that alters the gut microbiota. The deficiency in SCFAs production in host has associated with type 2 diabetes by interfering HbA1c levels in circulation [69]. Diet plat a major role in gut microbiota composition and gut microbiota regulates metabolism via metabolites produces by plant-based diets and intake of probiotics increases secretion of carbohydrate-active enzymes [70] in luminal of GIT.


4. Conclusion

Dietary fibers and its gut microbial metabolite SCFAs have been known to exert metabolic benefits to the host [71]. Various health benefits have been reported whereby Dietary fibers via SCFA increase plasma SCFA levels to active FFAR3 which has been shown to improve hepatic metabolic conditions. Furthermore, Dietary fibers consumption reduced HFD-induced liver weight growth and hepatic TG accumulation, as well as a shift in hepatic lipid metabolism. Dietary SCFAs consumption improved hepatic metabolic conditions via the FFAR3 signaling pathway. Besides, Dietary fibers were reported to shift the gut microbiome towards the production of more butanoate which is accompanied by up-regulation of microbiota and AMP-activated protein kinase (AMPK)-dependent gene expression which contributes to intestinal integrity and homeostasis by affecting metabolism, transporter expression. In addition, microbial metabolite SCFAs derived from microbial fermentation of dietary fibers are likely to have more broad impacts on various aspects of host physiology including health. Hence, Diet plays a pivotal role and is key as they have a significant impact on the composition, variety, and richness of the gut microbiota which directly determines the formation of essential SCFAs metabolites. Different aspects of the diet have a time-dependent effect on gut bacterial ecosystems. Long-term dietary patterns, particularly high protein and animal fat intake, have been demonstrated to diminish the number of beneficial microorganisms, which has been linked to host health.


Conflict of interest

The authors declare no competing interest.


Author contributions

The authors’ responsibilities were as follows- Kavita Rani, Jitendra Kumar, S. Sangwan, Nampher Masharing, M.D. Mitra and H.B. Singh conceived and designed the chapter. Draft was completed by Kavita Rani, Jitendra Kumar, Nampher Masharing.


Notes/thanks/other declarations

We would like to acknowledge the support from the Director, ICAR-National Dairy Research Institute, Karnal-132,001, Haryana, India.


  1. 1. Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, Brown D, Stares MD, Scott P, Bergerat A, Louis P. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. The ISME journal. 2011;5(2):220-230
  2. 2. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World journal of gastroenterology: WJG. 2015 7;21(29):8787
  3. 3. Laterza L, Rizzatti G, Gaetani E, Chiusolo P, Gasbarrini A. The gut microbiota and immune system relationship in human graft-versus-host disease. Mediterranean journal of hematology and infectious diseases. 2016; 8(1)
  4. 4. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS biology. 2016 19;14(8):e1002533
  5. 5. Gentile CL, Weir TL. The gut microbiota at the intersection of diet and human health. Science. 2018 Nov 16;362(6416):776-780
  6. 6. Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki SI, Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol. 2008 1;59 (Suppl 2):251-62
  7. 7. Deehan EC, Duar RM, Armet AM, Perez-Munoz ME, Jin M, Walter J. Modulation of the gastrointestinal microbiome with nondigestible fermentable carbohydrates to improve human health. Microbiology spectrum. 2017;5(5):5-
  8. 8. Lovegrove A, Edwards CH, De Noni I, Patel H, El SN, Grassby T, Zielke C, Ulmius M, Nilsson L, Butterworth PJ, Ellis PR. Role of polysaccharides in food, digestion, and health. Critical reviews in food science and nutrition. 2017;57(2):237-253
  9. 9. Deehan EC, Walter J. The fiber gap and the disappearing gut microbiome: implications for human nutrition. Trends in Endocrinology & Metabolism. 2016; 27(5):239-242
  10. 10. Bindels LB, Delzenne NM, Cani PD, Walter J. Towards a more comprehensive concept for prebiotics. Nature reviews Gastroenterology & hepatology. 2015; 12(5):303
  11. 11. Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016; 165(6):1332-1345
  12. 12. Schroeder BO, Birchenough GM, Ståhlman M, Arike L, Johansson ME, Hansson GC, Bäckhed F. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell host & microbe. 2018; 23(1):27-40
  13. 13. Zou J, Chassaing B, Singh V, Pellizzon M, Ricci M, Fythe MD, Kumar MV, Gewirtz AT. Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell host & microbe. 2018; 23(1):41-53
  14. 14. Laterza L, Rizzatti G, Gaetani E, Chiusolo P, Gasbarrini A. The gut microbiota and immune system relationship in human graft-versus-host disease. Mediterranean journal of hematology and infectious diseases. 2016; 8(1)
  15. 15. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M. Enterotypes of the human gut microbiome. nature. 2011;473(7346):174-180
  16. 16. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut microbes. 2012;3(4):289-306
  17. 17. Martínez I, Kim J, Duffy PR, Schlegel VL, Walter J. Resistant starches types 2 and 4 have differential effects on the composition of the fecal microbiota in human subjects. PloS one. 2010;5(11):e15046
  18. 18. Davis LM, Martínez I, Walter J, Goin C, Hutkins RW. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. PLoS One. 2011;6(9):e25200
  19. 19. Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, Fu H, Xue X, Lu C, Ma J, Yu L. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018 ; 359(6380):1151-1156
  20. 20. Macfarlane GT, Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. Journal of AOAC International. 2012 Jan 1;95(1):50-60
  21. 21. Cummings J, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987 Oct 1;28(10):1221-1227
  22. 22. Cummings JH, Macfarlane GT. The control and consequences of bacterial fermentation in the human colon. Journal of Applied Bacteriology. 1991;70(6):443-459
  23. 23. Wall R, Ross RP, Shanahan F. O Mahony L, O Mahony C, Coakley M, et al. Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am J Clin Nutr. 2009;89(5):1393-1401
  24. 24. Russell WR, Gratz SW, Duncan SH, Holtrop G, Ince J, Scobbie L, Duncan G, Johnstone AM, Lobley GE, Wallace RJ, Duthie GG. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. The American journal of clinical nutrition. 2011;93(5):1062-1072
  25. 25. Smith EA, Macfarlane GT. Dissimilatory amino acid metabolism in human colonic bacteria. Anaerobe. 1997;3(5):327-337
  26. 26. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell metabolism. 2009 ;9(4):311-326
  27. 27. Hetzel M, Brock M, Selmer T, Pierik AJ, Golding BT, Buckel W. Acryloyl-CoA reductase from Clostridium propionicum: An enzyme complex of propionyl-CoA dehydrogenase and electron-transferring flavoprotein. European journal of biochemistry. 2003;270(5):902-910
  28. 28. Scott KP, Martin JC, Campbell G, Mayer CD, Flint HJ. Whole-genome transcription profiling reveals genes up-regulated by growth on fucose in the human gut bacterium “Roseburia inulinivorans”. Journal of bacteriology. 2006; 188(12):4340-4349
  29. 29. Louis P, Duncan SH, McCrae SI, Millar J, Jackson MS, Flint HJ. Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. Journal of bacteriology. 2004;186(7):2099-2106
  30. 30. Duncan SH, Barcenilla A, Stewart CS, Pryde SE, Flint HJ. Acetate utilization and butyryl coenzyme A (CoA): acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Applied and environmental microbiology. 2002;68(10):5186-5190
  31. 31. Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta) genomic data. MBio. 2014;5(2):e00889-e00814
  32. 32. Tirosh A, Calay ES, Tuncman G, Claiborn KC, Inouye KE, Eguchi K, Alcala M, Rathaus M, Hollander KS, Ron I, Livne R. The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans. Science translational medicine. 2019;11(489)
  33. 33. Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proceedings of the Nutrition Society. 2003;62(1):67-72
  34. 34. King DE, Mainous III AG, Lambourne CA. Trends in dietary fiber intake in the United States, 1999-2008. Journal of the Academy of Nutrition and Dietetics. 2012;112(5):642-648
  35. 35. Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki SI, Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol. 2008;59(Suppl 2):251-262
  36. 36. Hong MY, Turner ND, Murphy ME, Carroll RJ, Chapkin RS, Lupton JR. In vivo regulation of colonic cell proliferation, differentiation, apoptosis, and P27Kip1 by dietary fish oil and butyrate in rats. Cancer prevention research. 2015;8(11):1076-1083
  37. 37. den Besten G, Lange K, Havinga R, van Dijk TH, Gerding A, van Eunen K, Muller M, Groen AK, Hooiveld GJ, € Bakker BM, et al. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am J Physiol Gastrointest Liver Physiol 2013; 305: G900-10; PMID: 24136789; ajpgi.00265.2013
  38. 38. Zaidi MS, Stocker CJ, O'Dowd J, Davies A, Bellahcene M, Cawthorne MA, Brown AJ, Smith DM, Arch JR. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short-chain fatty acids. FEBS letters. 2010;584(11):2381-2386
  39. 39. Demigne C, Morand C, Levrat MA, Besson C, Moundras C, Remesy C. Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes. Br J Nutr 1995; 74:209-219; PMID: 7547838;
  40. 40. Liou AP, Paziuk M, Luevano JM, Jr., Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med 2013; 5:178ra41; PMID: 23536013;
  41. 41. Layden BT, Yalamanchi SK, Wolever TM, Dunaif A, Lowe WL, Jr. Negative association of acetate with visceral adipose tissue and insulin levels. Diabetes Metab Syndr Obes 2012; 5:49-55; PMID:22419881; 10.2147/DMSO.S29244
  42. 42. Zaibi MS, Stocker CJ, O'Dowd J, Davies A, Bellahcene M, MA, Brown AJ, Smith DM, Arch JR. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett 2010; 584:2381-6; PMID: 20399779; 10.1016/j.febslet.2010.04.027
  43. 43. Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, Petersen KF, Kibbey RG, Goodman AL, Shulman GI. Acetate mediates a microbiome-brain-β- cell axis to promote metabolic syndrome. Nature, 2016, doi:10.1038/nature18309
  44. 44. Tuncil, Y.E., Thakkar, R.D., Marcia, A.D.R., Hamaker, B.R. and Lindemann, S.R., 2018. Divergent short-chain fatty acid production and succession of colonic microbiota arise in fermentation of variously-sized wheat bran fractions. Scientific reports, 8(1), pp.1-13
  45. 45. Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T. and Mende, D.R., 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464(7285), pp.59-65
  46. 46. De Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I.B., La Storia, A., Laghi, L., Serrazanetti, D.I., Di Cagno, R., Ferrocino, I., Lazzi, C. and Turroni, S., 2016. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut, 65(11), pp.1812-1821
  47. 47. Sonnenburg, E.D., Smits, S.A., Tikhonov, M., Higginbottom, S.K., Wingreen, N.S. and Sonnenburg, J.L., 2016. Diet-induced extinctions in the gut microbiota compound over generations. Nature, 529(7585), pp.212-215
  48. 48. Duncan, S.H., Russell, W.R., Quartieri, A., Rossi, M., Parkhill, J., Walker, A.W. and Flint, H.J., 2016. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid. Environmental microbiology, 18(7), pp.2214-2225
  49. 49. Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, Ballet V, Claes K, Van Immerseel F, Verbeke K, Ferrante M. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. 2014;63(8):1275-1283
  50. 50. Kim HJ, Bae SC. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. American journal of translational research. 2011; 3(2):166
  51. 51. MacDonald VE, Howe LJ. Histone acetylation: where to go and how to get there. Epigenetics. 2009 ;4(3):139-143
  52. 52. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein–coupled receptor FFAR2. Diabetes. 2012;61(2):364-371
  53. 53. Tazoe H, Otomo Y, Karaki SI, Kato I, Fukami Y, Terasaki M, Kuwahara A. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomedical research. 2009;30(3):149-156
  54. 54. Kendrick SF, O'Boyle G, Mann J, Zeybel M, Palmer J, Jones DE, Day CP. Acetate, the key modulator of inflammatory responses in acute alcoholic hepatitis. Hepatology. 2010;51(6):1988-1997
  55. 55. Usami M, Kishimoto K, Ohata A, Miyoshi M, Aoyama M, Fueda Y, Kotani J. Butyrate and trichostatin A attenuate nuclear factor κB activation and tumor necrosis factor α secretion and increase prostaglandin E2 secretion in human peripheral blood mononuclear cells. Nutrition research. 2008;28(5):321-328
  56. 56. Xiong Y, Miyamoto N, Shibata K, Valasek MA, Motoike T, Kedzierski RM, Yanagisawa M. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proceedings of the National Academy of Sciences. 2004;101(4):1045-1050
  57. 57. Kang I, Kim SW, Youn JH. Effects of nicotinic acid on gene expression: potential mechanisms and implications for wanted and unwanted effects of the lipid-lowering drug. The Journal of Clinical Endocrinology & Metabolism. 2011 Oct 1;96(10):3048-3055
  58. 58. Shimizu H, Masujima Y, Ushiroda C, Mizushima R, Taira S, Ohue-Kitano R, Kimura I. Dietary short-chain fatty acid intake improves the hepatic metabolic condition via FFAR3. Scientific reports. 2019;9(1):1-0
  59. 59. Gao, X., Lin, S.H., Ren, F., Li, J.T., Chen, J.J., Yao, C.B., Yang, H.B., Jiang, S.X., Yan, G.Q ., Wang, D. and Wang, Y., 2016. Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia. Nature communications, 7(1), pp.1-14
  60. 60. Martin AM, Lumsden AL, Young RL, Jessup CF, Spencer NJ, Keating DJ. The nutrient-sensing repertoires of mouse enterochromaffin cells differ between duodenum and colon. Neurogastroenterology & Motility. 2017;29(6):e13046
  61. 61. Dumont Y, Fournier A, St-Pierre S, Quirion R. Characterization of neuropeptide Y binding sites in rat brain membrane preparations using [125I][Leu31, Pro34] peptide YY and [125I] peptide YY3-36 as selective Y1 and Y2 radioligands. Journal of Pharmacology and Experimental Therapeutics. 1995; 272(2):673-680
  62. 62. Loh K, Herzog H, Shi YC. Regulation of energy homeostasis by the NPY system. Trends in Endocrinology & Metabolism. 2015; 26(3):125-135
  63. 63. Lin HV, Frassetto A, Kowalik Jr EJ, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PloS one. 2012;7(4)
  64. 64. Grøndahl MF, Keating DJ, Vilsbøll T, Knop FK. Current Therapies That Modify Glucagon Secretion: What Is the Therapeutic Effect of Such Modifications?. Current diabetes reports. 2017;17(12):128
  65. 65. Holst JJ. The physiology of glucagon-like peptide 1. Physiological reviews. 2007 ;87(4):1409-1439
  66. 66. Sileikiene V, Mosenthin R, Bauer E, Piepho HP, Tafaj M, Kruszewska D, Weström B, Erlanson-Albertsson C, Pierzynowski SG. Effect of ileal infusion of short-chain fatty acids on pancreatic prandial secretion and gastrointestinal hormones in pigs. Pancreas. 2008;37 (2):196-202
  67. 67. Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, Offermanns S. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nature medicine. 2015;21(2):173
  68. 68. Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T, Takahashi T. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nature communications. 2013 May 7;4(1):1-2. PMID: 23652017;
  69. 69. Zhao, L., Zhang, F., Ding, X., Wu, G., Lam, Y.Y., Wang, X., Fu, H., Xue, X., Lu, C., Ma, J. and Yu, L., 2018. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 359(6380), pp.1151-1156
  70. 70. David LA, Maurice CF, Carmody RN, Gootengerg DB, Button JE, Wolfe B. & Turnbaugh, PJ (2013). Diet rapidly and reproducibly alters the human gut microbiome. Nature.;505:7484
  71. 71. Kumar J, Rani K, Datt C. Molecular link between dietary fibre, gut microbiota and health. Molecular Biology Reports. 2020; 4:1-9

Written By

Kavita Rani, Jitendra Kumar, Sonia Sangwan, Nampher Masharing, Murli Dhar Mitra and H.B. Singh

Submitted: June 27th, 2021 Reviewed: July 21st, 2021 Published: September 24th, 2021