Role Of Short-chain Fatty Acids Research Articles

Biological significance of short-chain fatty acid metabolism by the intestinal microbiome

Evidence suggests that short-chain fatty acids (SCFAs) derived from microbial metabolism in the gut play a central role in host homeostasis. The present review describes the current understanding and physiological implications of SCFAs derived from microbial metabolism of nondigestible carbohydrates. Recent studies indicate a role for SCFAs, in particular propionate and butyrate, in metabolic and inflammatory disorders such as obesity, diabetes and inflammatory bowel diseases, through the activation of specific G-protein-coupled receptors and modification of transcription factors. Established prebiotics, such as fructooligosaccharides and galactooligosaccharides, which support the growth of Bifidobacteria, mainly mediate acetate production. Thus, recent identification of prebiotics which are able to stimulate the production of propionate and butyrate by benign saccharolytic populations in the colon is of interest. Manipulation of saccharolytic fermentation by prebiotic substrates is beginning to provide information on structure-function relationships relating to the production of SCFAs, which have multiple roles in host homeostasis.

The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism.

Chapter Three - Regulation of Bacterial Pathogenesis by Intestinal Short-Chain Fatty Acids

The human gut microbiota is inextricably linked to health and disease. One important function of the commensal organisms living in the intestine is to provide colonization resistance against invading enteric pathogens. Because of the complex nature of the interaction between the microbiota and its host, multiple mechanisms likely contribute to resistance. In this review, we dissect the biological role of short-chain fatty acids (SCFA), which are fermentation end products of the intestinal microbiota, in host-pathogen interactions. SCFA exert an extensive influence on host physiology through nutritional, regulatory, and immunomodulatory functions and can also affect bacterial fitness as a form of acid stress. Moreover, SCFA act as a signal for virulence gene regulation in common enteric pathogens. Taken together, these studies highlight the importance of the chemical environment where the biology of the host, the microbiota, and the pathogen intersects, which provides a basis for designing effective infection prevention and control.

A Novel Antiinflammatory Role for the Short-Chain Fatty Acids in Human Labor

Human parturition is an inflammatory process that can be activated prematurely by pathological stimuli. This study investigated the expression of G protein-coupled receptors GPR43 and GPR41 receptors in human uteroplacental tissues and the role of short-chain fatty acids (SCFA) in modulating inflammatory pathways in fetal membranes. Expression of GPR43 and GPR41 was investigated in uteroplacental tissues collected from women delivering at term or preterm after ethical approval and patient informed consent. The effect of SCFA on expression of inflammatory genes was assessed in amnion explants after culture with a mimetic of infection (lipopolysaccharide, LPS). Sodium propionate effect on LPS-induced neutrophil chemotaxis was evaluated by transwell assay. GPR43 and GPR41 mRNA expression was higher in myometrium and fetal membranes collected from women after the onset of labor. GPR43 protein expression localized to immune cells and vascular endothelium in the myometrium and epithelium of fetal membranes. Treatment with LPS significantly increased mRNA expression of GPR43 and inflammatory genes. Cotreatment with LPS and sodium propionate decreased LPS-induced expression of inflammatory genes including IL-6, IL-8, cyclooxygenase-2, IL-1α, intercellular adhesion molecule-1, and platelet endothelial cell adhesion molecule-1 but not IL-1β or lymphocyte function-associated antigen-1. Sodium propionate reduced LPS-induced neutrophil chemotaxis and protein secretion of the neutrophil chemoattractant IL-8. Finally, fetal membrane expression of GPR43 was significantly higher in women delivering preterm with evidence of infection. GPR43-SCFA interactions may represent novel pathways that regulate inflammatory processes involved in human labor. Suppression of inflammatory pathways by SCFA may be therapeutically beneficial for pregnant women at risk of pathogen-induced preterm delivery.

A novel facet to consider for the effects of butyrate on its target cells. Focus on “The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein”

short-chain fatty acids (SCFAs), acetate, propionate, and butyrate are produced by bacterial fermentation of dietary fiber in the colonic lumen. In the normal human large intestine, SCFA concentrations range from 70 to 100 mM; these SCFAs account for ∼80% of the anions present in the lumen ([5][1

Intestinal health functions of colonic microbial metabolites: a review

This review tries to find a scientific answer on the following two questions: (1) to what extent do we understand the specific role of colonic microbial metabolites, especially short-chain fatty acids (SCFA), in maintaining the health status and prevention of diseases of the colon and the host; (2) to what extent can we influence or even control the formation of colonic microbial metabolites which are beneficial for the health status. The review focuses on the following topics: energy source, intestinal motility, defence barrier, oxidative stress with special attention for antiinflammatory and anti-carcinogen functions, and satiety. Also the risk of overproduction of SCFA is discussed. Reviewing the literature as present today, it can be concluded that physiological levels of SCFA are vital for the health and well-being of the host and that the presence of carbohydrates (dietary fibre, prebiotics) is essential to favour the metabolic activity in the direction of carbohydrate fermentation. For optimal motor activity of the ileum and colon, to regulate the physiological intestinal mobility, steadily fermentable dietary fibres or prebiotics are crucial. The formation of SCFA, especially propionate and butyrate, up to high physiological levels in the colon, much likely also contributes to the defence mechanisms of the intestinal wall. No final answer can be given yet about the role of SCFA in anti-inflammation and anti-carcinogenicity, but recently published research shows possible mechanisms in this field. The intake of prebiotics or specific dietary fibres promotes the formation of SCFA within the physiological range, and more or less specifically increases the levels of propionate and butyrate. In this way, they provide benefit to the host, especially the natural regulation of the digestive system.

Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41)

The maintenance of energy homeostasis is essential for life, and its dysregulation leads to a variety of metabolic disorders. Under a fed condition, mammals use glucose as the main metabolic fuel, and short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber also contribute a significant proportion of daily energy requirement. Under ketogenic conditions such as starvation and diabetes, ketone bodies produced in the liver from fatty acids are used as the main energy sources. To balance energy intake, dietary excess and starvation trigger an increase or a decrease in energy expenditure, respectively, by regulating the activity of the sympathetic nervous system (SNS). The regulation of metabolic homeostasis by glucose is well recognized; however, the roles of SCFAs and ketone bodies in maintaining energy balance remain unclear. Here, we show that SCFAs and ketone bodies directly regulate SNS activity via GPR41, a Gi/o protein-coupled receptor for SCFAs, at the level of the sympathetic ganglion. GPR41 was most abundantly expressed in sympathetic ganglia in mouse and humans. SCFA propionate promoted sympathetic outflow via GPR41. On the other hand, a ketone body, β-hydroxybutyrate, produced during starvation or diabetes, suppressed SNS activity by antagonizing GPR41. Pharmacological and siRNA experiments indicated that GPR41-mediated activation of sympathetic neurons involves Gβγ-PLCβ-MAPK signaling. Sympathetic regulation by SCFAs and ketone bodies correlated well with their respective effects on energy consumption. These findings establish that SCFAs and ketone bodies directly regulate GPR41-mediated SNS activity and thereby control body energy expenditure in maintaining metabolic homeostasis.

Short chain fatty acids may elicit an innate immune response from preadipocytes: A potential link between bacterial infection and inflammatory diseases

Short chain fatty acids (SCFAs) such as acetate, propionate and butyrate are produced by bacterial fermentation of dietary fiber. The highest concentrations of SCFAs in the body are found in the colon. Elevated dietary acetate has been shown to have anti-inflammatory effects in mouse models of colitis and inflammatory diseases in peripheral tissues. The details of how dietary SCFAs stimulate reduced inflammation in peripheral tissues have not been determined. I suggest that SCFA concentrations in peripheral tissues are generally not sufficient to locally produce a significant anti-inflammatory effect from immune cells. Moreover it is possible that elevated SCFA levels in peripheral tissues may actually stimulate an inflammatory response. The hypothesis is presented that preadipocytes and other cells with immune function such as fibroblasts in peripheral tissues elicit an inflammatory innate immune response when exposed to SCFAs at millimolar concentrations. A role for SCFAs in activating an immune response in preadipocytes is possible given the expression of a SCFA receptor in these cells, the demonstration that adipocytes and preadipocytes have immunity related functions, the observation that 2 mM SCFAs stimulated the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA from 3T3-L1 preadipocytes and that concentrations of SCFAs can reach elevated levels at sites of bacterial infection. A SCFA-induced inflammatory response from preadipocytes and other cells with immune function, such as fibroblasts, may provide a further contributing factor linking bacterial infection to the development of insulin resistance and the severity of inflammatory diseases such as atherosclerosis.

Abstract A20: Evidences that GPR43, a G-protein-coupled receptor for short chain fatty acids, suppresses colon cancer

Abstract GPR43 is a G protein-coupled receptor for short chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In this study, we show that SCFAs also exert their anti-tumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues (N=31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues (N=70) and their corresponding lymph node metastatic adenocarcinomas (N =38). RT-PCR analysis detected the presence of full length GPR43 mRNA in only one (HT-29) out of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin-dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA-induced cell proliferation inhibition and apoptotic cell death in colon cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A20.

G‐protein‐coupled receptor for short‐chain fatty acids suppresses colon cancer

GPR43 is a G-protein-coupled receptor for short-chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In our study, we show that SCFAs also exert their antitumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues (N = 31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues (N = 70) and their corresponding lymph node metastatic adenocarcinomas (N = 38). RT-PCR analysis detected the presence of full length GPR43 mRNA in only one (HT-29) of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin-dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA-induced cell proliferation inhibition and apoptotic cell death in colon cancer.

Roles of Short-Chain Fatty Acids and their Receptors in Colonic Motility

Short chain fatty acids (SCFAs) are major anions in the large intestine. They are produced by bacterial fermentation of dietary fiber. However, the mechanism by which intraluminal SCFAs are sensed is unknown. Free fatty acids including SCFAs have recently been demonstrated to act as ligands for several G-protein-coupled receptors (GPCRs: FFA1, FFA2, FFA3, GPR84, GPR109A and GPR120). SCFAs are ligands for FFA2 and FFA3. These receptors are proposed to play a variety of physiological and pathophysiological roles in the intestine. In rat and human colons, FFA2 and/or FFA3 are located in mucosal enteroendocrine cells containing peptide YY (PYY) and are related to energy balance. Among SCFAs, propionate and butyrate induce concentration-dependent phasic and tonic contractions in rat colonic circular muscle. These responses are not observed in mucosal free preparations. Thus, FFA2 and FFA3 are important molecular devices for monitoring the chemical composition in the colonic lumen. For the local function of SCFAs, it should be stressed that individual SCFAs have different modes of action on colonic smooth muscles. These different actions may be due to the relative contributions of FFA2 and FFA3 to the control of intestinal muscle activity. FFA2 and FFA3 may also contribute to the whole body energy balance through the release of gastrointestinal hormones related to feeding and satiety control. This review summarizes recent findings about the roles of deorphanized FFA receptors, especially, FFA2 and FFA3 and their contributions to the regulation of colonic motility.

Short-chain fatty acids modulate gene expression for vascular endothelial cell adhesion molecules

Objective Leukocyte infiltration into the intestinal wall is central to the pathogenesis of tissue injury that occurs in patients with a variety of inflammatory bowel diseases. Migration of leukocytes from the intestinal circulation into bowel tissues is mediated by chemotactic substances and adhesion molecules (i.e., intercellular adhesion molecule-1 [ICAM-1] and E-selectin) on the surface of endothelial cells lining blood vessels. Short-chain fatty acids (SCFAs) derived from dietary fiber decrease inflammatory responses in colon cells. However, the effect of SCFAs on vascular adhesion molecules is unknown. We investigated the effects of SCFAs on vascular endothelial cell adhesion molecule expression. Methods We assessed the effect of physiologically relevant concentrations of butyrate on expression of ICAM-1 protein and mRNA in cultures of human umbilical vein endothelial cells. We also assessed the effect of butyrate on levels of HLA-DR, E-selectin, vascular cell adhesion molecule-1, and endoglin. In additional experiments, we evaluated the effect of butyrate on ICAM-1 mRNA stability and the effect of valerate, isobutyrate, and propionate on ICAM-1 expression. The effect of butyrate on ICAM-1 expression was compared with that of trichostatin A, a specific inhibitor of histone deacetylase. Data were evaluated with Student’s t tests or Tukey’s multiple comparison tests, with P < 0.05 considered statistically significant. Results Butyrate concentrations of 2.5 to 5 mM significantly increased endothelial expressions of ICAM-1 protein and mRNA. The effect of butyrate (5 mM) on ICAM-1 expression was time dependent, with significant increases in levels occurring after 16 h of incubation. Butyrate (5 mM) also increased expression of E-selectin but not of HLA-DR, vascular cell adhesion molecule-1, or endoglin. Isobutyrate had little effect on ICAM-1 expression, whereas valerate and propionate significantly increased expression of ICAM-1 but were weaker stimulants compared with butyrate. Butyrate (5 mM) did not alter stability of ICAM-1 mRNA. The effect of butyrate (5 mM) was comparable to that of trichostatin A. The stimulatory effect of butyrate on ICAM-1 expression was reversed after 48 h of butyrate withdrawal. Conclusions Butyrate increases vascular endothelial expressions of ICAM-1 and E-selectin. We speculate that butyrate-induced effects on vascular adhesion molecules modulate gut inflammation. The role of SCFAs and fiber in the pathogenesis and modulation of gut inflammation in vivo requires further study.

Role of short-chain fatty acids in colonic HCO3secretion

Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO(3) secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO(3) secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO(3) secretion was measured in isolated colonic mucosa mounted in Lucite chambers using pH stat technique and during microperfusion of isolated colonic crypts. (14)C-labeled butyrate, (14)C-labeled isobutyrate, and (36)Cl uptake were also determined by apical membrane vesicles (AMV) isolated from surface and/or crypt cells. Butyrate stimulation of Cl-independent, DIDS-insensitive 5-nitro-3-(3-phenylpropyl-amino)benzoic acid-insensitive HCO(3) secretion is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO(3) secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO(3) secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO(3) secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO(3) secretion in isolated microperfused crypts, whereas an outward-directed HCO(3) gradient-driven induced (14)C-butyrate uptake by surface but not crypt cell AMV. Both (36)Cl/HCO(3) exchange and potential-dependent (36)Cl movement in AMV were inhibited by 96-98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO(3) secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO(3) exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO(3) secretion is most likely a result of an apical membrane SCFA/HCO(3) exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO(3) secretion secondary to SCFA inhibition of apical membrane Cl/HCO(3) exchange and anion channel activity, respectively.

Luminal bacterial flora determines physiological expression of intestinal epithelial cytoprotective heat shock proteins 25 and 72

Heat shock proteins (HSP) 25 and 72 are expressed normally by surface colonocytes but not by small intestinal enterocytes. We hypothesized that luminal commensal microflora maintain the observed colonocyte HSP expression. The ability of the small intestine to respond to bacteria and their products and modulate HSPs has not been determined. The effects of luminal bacterial flora in surgically created midjejunal self-filling (SFL) vs. self-emptying (SEL) small-bowel blind loops on epithelial HSP expression were studied. HSP25 and HSP72 expression were assessed by immunoblot and immunohistochemistry. SFL were chronically colonized, whereas SEL contained levels of bacteria normal for the proximal small intestine. SFL creation significantly increased HSP25 and HSP72 expression relative to corresponding sections from SEL. Metronidazole treatment, which primarily affects anaerobic bacteria as well as a diet lacking fermentable fiber, significantly decreased SFL HSP expression. Small bowel incubation with butyrate ex vivo induced a sustained and significant upregulation of HSP25 and altered HSP72 expression, confirming the role of short-chain fatty acids. To determine whether HSPs induction altered responses to an injury, effects of the oxidant, monochloramine, on epithelial resistance and short-circuit current (I(sc)) responses to carbachol and glucose were compared. Increased SFL HSP expression was associated with protection against oxidant-induced decreases in transmural resistance and I(sc) responses to glucose, but not secretory responses to carbachol. In conclusion, luminal microflora and their metabolic byproducts direct expression of HSPs in gut epithelial cells, an effect that contributes to preservation of epithelial cell viability under conditions of stress.

Orientation Behaviour of the Blood-sucking Bug Triatoma infestans to Short-chain Fatty Acids: Synergistic Effect of L-Lactic Acid and Carbon Dioxide

The role of short-chain fatty acids in the host-seeking behaviour of Triatoma infestans larvae was investigated using a locomotion compensator. Several short-chain fatty acids were tested alone over a wide range of doses, or in combination with L-lactic acid (L-LA; 100 microg). Bugs showed no attractive response to single carboxylic acids, but when L-LA was added to airstreams carrying specific intensities of either propionic (C3; 100 microg), butyric (C4; 1 microg) or valeric acid (C5; 1 microg), these mixtures elicited an attractive response, evincing a synergistic effect. No orientation response was observed when caproic acid (C6) was offered with L-LA at the doses tested. Two blends were created: (1) C3, C4 and C5 combined at the effective doses when added with L-LA [C3C4C5 (1)], and (2) C3, C4 and C5 combined at a third of those intensities [C3C4C5 (2)]. Both blends were tested alone, with L-LA (100 microg), with a sub-threshold concentration of CO(2) (300 p.p.m. above the ambient level), and combined with both compounds together. Oriented responses of bugs were only observed with the blend (2) added with L-LA and with the combination of this lure with CO(2). This last combination evoked a behavioural response similar in intensity to that induced by a live mouse.

Short Chain Fatty Acids, Menaquinones and Ubiquinones and Their Effects on the Host

The main effects on the host of some extracellular bacterial products, short-chain fatty acids (SCFAs), menaquinones and ubiquinones, are described in this paper. While few data are available on menaquinone and ubiquinone effects on mammalian cell properties, a vast literature exists on SCFAs. They are major by-products of anaerobic fermentation of unabsorbed starch and non-starch polysaccharides (i.e., dietary plant fibers) and constitute approximately two-thirds of the colon anion concentration. The term SCFAs refers to a group of C 2 -C 6 mono-carboxylic acids, but of these compounds the major SCFAs involved in mammalian physiology are the straight chain fatty acid acetate c2, propionate c3 and butyrate c4. Data are briefly reviewed regarding the production of SCFAs, their role in the maintenance of human intestinal ‘mucosal health’, their implication in the pathogenesis of several diseases and their controversial effects on colon cancer and polyps. The role of SCFAs as virulence factors of anaerobic bacteria (effect in the pathogenesis of periodontal diseases and impairment of phagocytic cell functions) is also discussed.

Effects of butyrate and propionate on the adhesion, growth, cell cycle kinetics, and protein synthesis of cultured human gingival fibroblasts.

Various periodontal and root canal pathogens, such as the Bacteroides species, can produce significant amounts of short chain fatty acids (SCFA). The roles of SCFA in the pathogenesis of periodontal disease are still not fully understood. We therefore investigated 2 main SCFA, butyrate and propionate, on the functional behavior of cultured human gingival fibroblasts (GF) such as cell growth, protein synthesis, cell adhesion capacity, and cell cycle progression. Butyrate and propionate inhibited the growth of healthy (HGF) and inflamed gingival fibroblasts (IGF) in a dose dependent manner. At concentrations of 4, 8, and 16 mM, butyrate suppressed the cell growth by 11 to 58%, 16 to 60%, and 50 to 71%, respectively. The response of cultured gingival fibroblasts to SCFA showed individual differences. Morphologically, GF became larger and more flattened in appearance following exposure to butyrate (>8 mM) and propionate (>24 mM) for 5 days. Inhibitory effects of butyrate (>2 mM) and propionate (>8 mM) on the growth of GF were due possibly to their inhibition of cell-cycle progression. At concentrations of 2 and 8 mM, butyrate led to G0/G1 arrest. Elevation of the exposure concentration to 8 to 24 mM further result in G2/M phase arrest of GF. On the other hand, propionate, at concentrations ranging from 4 to 24 mM, led to G0/G1 arrest. Butyrate (>2 mM) inhibited the proline-rich protein synthesis of GF. At concentrations of 4, 8, 16, and 24 mM, butyrate inhibited the protein synthesis of HGF-1 by 42%, 43%, 51%, and 54%, respectively. In all strains of cultured GF, the suppressive effect of propionate is less than that of butyrate. At concentration range of 4 to 24 mM, propionate suppressed the protein synthesis of HGF-1 by 23 to 43%. However, both butyrate and propionate (4 to 48 mM) exerted little effects on the adhesion of GF to type I collagen within 3 hours of incubation. These results suggested that SCFA released by pathogenic microorganisms can contribute to the gingival tissue dysfunction and breakdown through their actions on specific biological functions of GF.

Role of the ileocecal junction in the motor response to intestinal resection

Extensive resections of the distal small intestine are associated with motor disruption in the proximal remnant. Luminal contents such as bacteria and short-chain fatty acids may play a role. We evaluated the effect of bypass of the ileocecal junction (ICJ) on the motor response to a 50% distal resection. Thirty-five dogs were divided into three groups: transection control (TC, n = 11); 50% distal resection with intact ICJ (DR, n = 12), and 50% distal resection with jejunocolostomy to bypass the ICJ (DRBP, n = 12). Motor activity, intestinal transit, nutrition, absorption, and motor active hormones were studied over a 3-month period. Caloric intake was reduced and nutritional status similarly impaired in both resected groups. Steatorrhea, however, was significantly greater after DRBP. Intestinal structural adaptation was similar in both resected groups at 12 weeks. Animals in the bypass group demonstrated elevated intraluminal short-chain fatty acid and anaerobic bacterial counts. Migrating motor complex frequency was similar in the three groups; distal starts, however, were more frequent in both resected groups. Clustered contractile activity was prominent in the remnant after both DR and DRBP (50% and 32% recording time occupied by clusters, respectively [not significant]). Basal levels of peptide YY were increased following resection and this increase was unaffected by ICJ bypass. Postprandial neurotensin concentrations were transiently increased after distal bowel resection. In contrast, the postprandial neurotensin response was abolished following resection with bypass of the ICJ. Basal motilin levels were reduced following resection alone but not after resection with ICJ bypass. The motor response to resection does not appear to be related to alterations in circulating levels of hormones localized to the distal ileum; neither does it seem to be influenced by luminal bacteria and short-chain fatty acids or retention of a sphincteric mechanism at the ICJ. These findings also raise questions about the role of short-chain fatty acids and bacteria in the generation of the various distinctive motor patterns of the distal ileum. Resection of the distal ileum through loss of the receptor site for either retarding reflexes or bile salt absorption may be of greater importance in determining the motor response to resection.

Role of short-chain fatty acids in the prevention of colorectal cancer.

Short-chain fatty acids (SCFAs: acetate, propionate, n-butyrate) arising in the large bowel during bacterial fermentation of dietary fibre and starch have paradoxical effects on colonic epithelial proliferation. While the three major SCFAs stimulate proliferation of normal crypt cells, n-butyrate and, to a lesser degree, propionate inhibit growth of colon cancer cell lines. At the molecular level, n-butyrate causes histone acetylation, favours differentiation, induces apoptosis and regulates the expression of various oncogenes. To understand the complex effects of SCFAs on carcinogenesis, it is important to study the intermediate stages of the adenoma-carcinoma sequence where a "switch" from stimulation to suppression of cell proliferation must occur.

Plasma short-chain fatty acids in fulminant hepatic failure

The role of short-chain fatty acids in the pathogenesis of coma in patients with fulminant hepatic failure has been studied by gas-liquid chromatography. There was no correlation between the initial or the final plasma levels of shortchain fatty acids in these patients and the clinical outcome of their disease. A primary role for the short-chain fatty acids in the pathogenesis of coma in fulminant hepatic failure is unlikely.