Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.

Yunpi Tongbian Fang alleviates slow transit constipation induced by loperamide by regulating intestinal microbiota and short-chain fatty acids in rats.

Slow transit constipation (STC) is a prevalent chronic colonic dysfunction disease that significantly impairs the quality of life for affected individuals. Yunpi Tongbian Fang (YPTBF), a traditional Chinese medicine compound, has demonstrated promising clinical efficacy; however, its underlying mechanism remains elusive. In order to assess the laxative properties of YPTBF, which encompasses the influence on gut microbiota, gut metabolites, gut neurotransmitters, and colon histology, an oral administration of YPTBF was conducted for a duration of two consecutive weeks on STC rats induced by loperamide hydrochloride. The results showed that YPTBF improved the symptoms of STC, alleviated the decrease in total fecal volume and fecal water content caused by loperamide-induced constipation, restored intestinal transport function, and HE staining showed the recovery of pathological damage to the colon mucosa. In addition, YPTBF increased the concentrations of 5-HT and ACHE, while reducing the concentrations of VIP and NO. YPTBF adjusted the diversity and abundance of gut microbiota in STC rats, enabling the recovery of beneficial bacteria and promoting the production of acetic acid, propionic acid, and butyric acid. We found that YPTBF can improve constipation in STC rats, possibly by regulating the intestinal microbiota structure and improving SCFAs metabolism.

Supplementation with SCFAs Re-Establishes Microbiota Composition and Attenuates Hyperalgesia and Pain in a Mouse Model of NTG-Induced Migraine.

Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine.

Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction.

BACKGROUND: 5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear. RESULTS: To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1ß, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1ß, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased. CONCLUSIONS: These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.

Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization.

Microglia activation and subsequent pro-inflammatory responses play a key role in the development of neuropathic pain. The process of microglia polarization towards pro-inflammatory phenotype often occurs during neuroinflammation. Recent studies have demonstrated an active role for the gut microbiota in promoting microglial full maturation and inflammatory capabilities via the production of Short-Chain Fatty Acids (SCFAs). However, it remains unclear whether SCFAs is involved in pro-inflammatory/anti-inflammatory phenotypes microglia polarization in the neuropathic pain. In the present study, chronic constriction injury (CCI) was used to induce neuropathic pain in mice, the mechanical withdrawal threshold, thermal hyperalgesia were accomplished. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), pro-inflammatory phenotype markers including CD68, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and anti-inflammatory phenotype markers including CD206, IL-4 in the hippocampus and spinal cord were determined on day 21 after CCI. The results showed that CCI produced mechanical allodynia and thermal hyperalgesia, and also increased the expressions of microglia markers (Iba1, CD11b) and pro-inflammatory phenotype markers (CD68, IL-1ß, and TNF-α), but not anti-inflammatory phenotype marker (CD206, IL-4) in the hippocampus and spinal cord, accompanied by increased SCFAs in the gut. Notably, antibiotic administration reversed these abnormalities, and its effects was also bloked by SCFAs administration. In conclusion, data from our study suggest that CCI can lead to mechanical and thermal hyperalgesia, while SCFAs play a key role in the pathogenesis of neuropathic pain by regulating microglial activation and subsequent pro-inflammatory phenotype polarization. Antibiotic administration may be a new treatment for neuropathic pain by reducing the production of SCFAs and further inhibiting the process of microglia polarization.

Effects of Short-Chain Fatty Acids on Human Oral Epithelial Cells and the Potential Impact on Periodontal Disease: A Systematic Review of In Vitro Studies.

Short-chain fatty acids (SCFA), bacterial metabolites released from dental biofilm, are supposed to target the oral epithelium. There is, however, no consensus on how SCFA affect the oral epithelial cells. The objective of the present study was to systematically review the available in vitro evidence of the impact of SCFA on human oral epithelial cells in the context of periodontal disease. A comprehensive electronic search using five databases along with a grey literature search was performed. In vitro studies that evaluated the effects of SCFA on human oral epithelial cells were eligible for inclusion. Risk of bias was assessed by the University of Bristol's tool for assessing risk of bias in cell culture studies. Certainty in cumulative evidence was evaluated using GRADE criteria (grading of recommendations assessment, development, and evaluation). Of 3591 records identified, 10 were eligible for inclusion. A meta-analysis was not possible due to the heterogeneity between the studies. The risk of bias across the studies was considered "serious" due to the presence of methodological biases. Despite these limitations, this review showed that SCFA negatively affect the viability of oral epithelial cells by activating a series of cellular events that includes apoptosis, autophagy, and pyroptosis. SCFA impair the integrity and presumably the transmigration of leucocytes through the epithelial layer by changing junctional and adhesion protein expression, respectively. SCFA also affect the expression of chemokines and cytokines in oral epithelial cells. Future research needs to identify the underlying signaling cascades and to translate the in vitro findings into preclinical models.

Differences in Fecal Gut Microbiota, Short-Chain Fatty Acids and Bile Acids Link Colorectal Cancer Risk to Dietary Changes Associated with Urbanization Among Zimbabweans.

The incidence of colorectal cancer (CRC) is gradually rising in sub-Saharan Africa. This may be due to dietary changes associated with urbanization, which may induce tumor-promoting gut microbiota composition and function. We compared fecal microbiota composition and activity in 10 rural and 10 urban Zimbabweans for evidence of a differential CRC risk. Dietary intake was assessed by a food frequency questionnaire. Fecal microbiota composition, metabolomic profile, functional microbial genes were analyzed, and bile acids and short chain fatty acids quantified. Animal protein intake was higher among urban volunteers, but carbohydrate and fiber intake were similar. Bacteria related to Blautia obeum, Streptococcus bovis, and Subdoligranulum variabile were higher in urban residents, whereas bacteria related to Oscillospira guillermondii and Sporobacter termitidis were higher in rural volunteers. Fecal levels of primary bile acids, cholic acid, and chenodeoxycholic acid (P < 0.05), and secondary bile acids, deoxycholic acid (P < 0.05) and ursodeoxycholic acid (P < 0.001) were higher in urban residents. Fecal levels of acetate and propionate, but not butyrate, were higher in urban residents. The gut microbiota composition and activity among rural and urban Zimbabweans retain significant homogeneity (possibly due to retention of dietary fiber), but urban residents have subtle changes, which may indicate a higher CRC risk.

Short-chain fatty acids increase TNFα-induced inflammation in primary human lung mesenchymal cells through the activation of p38 MAPK.

Short-chain fatty acids (SCFAs), produced as by-products of dietary fiber metabolism by gut bacteria, have anti-inflammatory properties and could potentially be used for the treatment of inflammatory diseases, including asthma. The direct effects of SCFAs on inflammatory responses in primary human lung mesenchymal cells have not been assessed. We investigated whether SCFAs can protect against tumor necrosis factor (TNF)α-induced inflammation in primary human lung fibroblasts (HLFs) and airway smooth muscle (ASM) cells in vitro. HLFs and ASM cells were exposed to SCFAs, acetate (C2:0), propionate (C3:0), and butyrate (C4:0) (0.01-25 mM) with or without TNFα, and the release of proinflammatory cytokines, IL-6, and CXCL8 was measured using ELISA. We found that none of the SCFAs suppressed TNFα-induced cytokine release. On the contrary, challenge with supraphysiological concentrations (10-25 mM), as might be used therapeutically, of propionate or butyrate in combination with TNFα resulted in substantially greater IL-6 and CXCL8 release from HLFs and ASM cells than challenge with TNFα alone, demonstrating synergistic effects. In ASM cells, challenge with acetate also enhanced TNFα-induced IL-6, but not CXCL8 release. Synergistic upregulation of IL-6 and CXCL8 was mediated through the activation of free fatty acid receptor (FFAR)3, but not FFAR2. The signaling pathways involved were further examined using specific inhibitors and immunoblotting, and responses were found to be mediated through p38 MAPK signaling. This study demonstrates that proinflammatory, rather than anti-inflammatory effects of SCFAs are evident in lung mesenchymal cells.

Antibiotic Exposure and Reduced Short Chain Fatty Acid Production after Hematopoietic Stem Cell Transplant.

Human studies have shown loss of diversity of the gut microbiome following hematopoietic stem cell transplantation (HSCT) in association with significant gut injury caused by the preparative regimen. Prolonged antibiotic use worsens loss of microbiome diversity and increases risk of complications such as graft-versus-host disease (GVHD). Our data support the hypothesis that loss of intestinal commensals that produce short-chain fatty acids (SCFAs) may increase dysbiosis. Here, we report an extensive longitudinal examination of changes in the luminal SCFAs in children undergoing allogeneic HSCT, and the relationship of those changes to the microbiota and antibiotic exposure. We found significant and progressive alterations in butyrate, and in additional SCFAs in stool in the first 14 days after transplant, a finding not observed in published mouse studies. SCFA levels were lower in children receiving antibiotics with activity against anaerobic organisms. Moreover, day 14 post-HSCT butyrate and propionate levels are lower in children who went on to develop GVHD, although our disease population was small. These data provide insight into the mechanism of prior observations that loss of diversity and increased antibiotic use are associated with GVHD following HSCT. Our findings offer potential modifiable targets to reduce risk of GVHD and improve survival after HSCT.

Comparing the effects of different dietary organic acids on the growth, intestinal short-chain fatty acids, and liver histopathology of red hybrid tilapia (Oreochromis sp.) and potential use of these as preservatives.

Dietary organic acids are increasingly being investigated as a potential means of improving growth and nutrient utilization in aquatic animals. A 9-week study was performed to compare equal amounts (2%) of different organic acids (sodium butyrate, acetate, propionate, or formate) on the growth, muscle proximate composition, fatty acid composition, cholesterol and lipid peroxidation, differential cell counts, plasma biochemistry, intestinal short-chain fatty acid (SCFA) level, and liver histopathology to red hybrid tilapia (Oreochromis sp.) (initial mean weight of 2.87 g). A second experiment was performed to determine their effects on lipid peroxidation and trimethylamine (TMA) when added at 1% to tilapia meat and left out for 24 h. The results of the first experiment showed no treatment effect to growth, feeding efficiencies, or muscle fatty acid composition, but all dietary organic acids significantly decreased intestinal SCFA. Dietary butyrate and propionate significantly decreased muscle lipid peroxidation compared to the control group, but the dietary formate treatment had the lowest lipid peroxidation compared to all treatments. Muscle crude protein and lipid in tilapia fed the formate diet were significantly lower and higher, respectively, and showed evidence of stress based on the differential cell counts, significantly higher plasma glucose and liver glycogen, as well as inflammatory responses in the liver. Although a potential benefit of dietary organic acids was a reduction to lipid peroxidation, this could be accomplished post-harvest by direct additions to the meat. In addition, inclusions of butyrate and propionate to tilapia meat significantly decreased TMA, which might be a more cost-effective option to improve the shelf life of tilapia products.

The association between dietary saturated fatty acids and ischemic heart disease depends on the type and source of fatty acid in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort.

BACKGROUND: The association between saturated fatty acid (SFA) intake and ischemic heart disease (IHD) risk is debated. OBJECTIVE: We sought to investigate whether dietary SFAs were associated with IHD risk and whether associations depended on 1) the substituting macronutrient, 2) the carbon chain length of SFAs, and 3) the SFA food source. DESIGN: Baseline (1993-1997) SFA intake was measured with a food-frequency questionnaire among 35,597 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. IHD risks were estimated with multivariable Cox regression for the substitution of SFAs with other macronutrients and for higher intakes of total SFAs, individual SFAs, and SFAs from different food sources. RESULTS: During 12 y of follow-up, 1807 IHD events occurred. Total SFA intake was associated with a lower IHD risk (HR per 5% of energy: 0.83; 95% CI: 0.74, 0.93). Substituting SFAs with animal protein, cis monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), or carbohydrates was significantly associated with higher IHD risks (HR per 5% of energy: 1.27-1.37). Slightly lower IHD risks were observed for higher intakes of the sum of butyric (4:0) through capric (10:0) acid (HRSD: 0.93; 95% CI: 0.89, 0.99), myristic acid (14:0) (HRSD: 0.90; 95% CI: 0.83, 0.97), the sum of pentadecylic (15:0) and margaric (17:0) acid (HRSD: 0.91: 95% CI: 0.83, 0.99), and for SFAs from dairy sources, including butter (HRSD: 0.94; 95% CI: 0.90, 0.99), cheese (HRSD: 0.91; 95% CI: 0.86, 0.97), and milk and milk products (HRSD: 0.92; 95% CI: 0.86, 0.97). CONCLUSIONS: In this Dutch population, higher SFA intake was not associated with higher IHD risks. The lower IHD risk observed did not depend on the substituting macronutrient but appeared to be driven mainly by the sums of butyric through capric acid, the sum of pentadecylic and margaric acid, myristic acid, and SFAs from dairy sources. Residual confounding by cholesterol-lowering therapy and trans fat or limited variation in SFA and PUFA intake may explain our findings. Analyses need to be repeated in populations with larger differences in SFA intake and different SFA food sources.

Examining acute and chronic effects of short- and long-chain fatty acids on peptide YY (PYY) gene expression, cellular storage and secretion in STC-1 cells.

PURPOSE: Peptide YY (PYY) is a gastrointestinal hormone with physiological actions regulating appetite and energy homoeostasis. The cellular mechanisms by which nutrients stimulate PYY secretion from intestinal enteroendocrine cells are still being elucidated. METHODS: This study comprehensively evaluated the suitability of intestinal STC-1 cells as an in vitro model of PYY secretion. PYY concentrations (both intracellular and in culture media) with other intestinal peptides (CCK, GLP-1 and GIP) demonstrated that PYY is a prominent product of STC-1 cells. Furthermore, acute and chronic PYY responses to 15 short (SCFAs)- and long-chain (LCFAs) dietary fatty acids were measured alongside parameters for DNA synthesis, cell viability and cytotoxicity. RESULTS: We found STC-1 cells to be reliable secretors of PYY constitutively releasing PYY into cell culture media (but not into non-stimulatory buffer). We demonstrate for the first time that STC-1 cells produce PYY mRNA transcripts; that STC-1 cells produce specific time- and concentration-dependent PYY secretory responses to valeric acid; that linoleic acid and conjugated linoleic acid 9,11 (CLA 9,11) are potent PYY secretagogues; and that chronic exposure of SCFAs and LCFAs can be detrimental to STC-1 cells. CONCLUSIONS: Our studies demonstrate the potential usefulness of STC-1 cells as an in vitro model for investigating nutrient-stimulated PYY secretion in an acute setting. Furthermore, our discovery that CLA directly stimulates L-cells to secrete PYY indicates another possible mechanism contributing to the observed effects of dietary CLA on weight loss.

Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.

Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet-cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15,351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6.0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2.00; 95 % CI 1.30, 3.09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.

In vitro effects of hydrochloric and lactic acids on bioelectric properties of equine gastric squamous mucosa.

REASONS FOR PERFORMING STUDY: Volatile fatty acids, byproducts of carbohydrate fermentation by resident bacteria, have been implicated in causing nonglandular (NG) gastric ulcers. Lactic acid (LA), also produced by stomach bacteria, may cause gastric ulcers when exposed to the equine NG mucosa. OBJECTIVES: To investigate the in vitro effects of LA on equine NG mucosa bioelectric properties, sodium transport and tissue resistance. METHODS: Gastric tissues obtained from 13 mature horses were studied in Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured, and electrical resistance (R) and conductance (G) calculated for tissues after addition of HCl and LA (5, 10, 20 and 40 mmol/l) in normal Ringer's solution (NRS). RESULTS: Mucosa exposed to HCl or LA (5, 10 and 20 mmol/l) in NRS (pH 1.5 and to a lesser extent pH 4.0) had a significant decrease in Isc and PD. Mucosa exposed to a high concentration of LA (40 mmol/l) in NRS (LRS) at pH 1.5 showed an increased G, but this increase was not significant. Values returned to baseline after solutions were returned to pH 7.0. Histological changes were consistent with HCl-induced (pH <4.0) acid damage. CONCLUSIONS: HCl induced alteration in bioelectric properties of equine NG mucosa whereas addition of LRS did not, other than those changes seen with HCl alone.

Alterações morfológicas induzidas por butirato, propionato e lactato sobre a mucosa ruminal e a epiderme de bezerros: I Aspectos histológicos / Lactate, propionate and, butyrate induced morphological alterations on calf ruminal mucosa and epidermis: I Histologycals aspects

Dezessete bezerros foram utilizados para avaliar o efeito de ácidos graxos voláteis (AGV) sobre a morfologia ruminal, a epiderme do plano nasolabial, a epicera e o perioplum, e para validar a execução de biópsias tegumentares como indicadores de alterações da mucosa ruminal. Os animais receberam infusões intra-ruminal de butirato, propionato, lactato ou salina (controle) durante 37 dias. A insulina sorológica foi dosada no 22º dia experimental nos tempos de 0, 90, 180 e 360 minutos em relação à infusão diária da manhã. No 89º dia de vida, após o abate, foram coletados fragmentos ruminais e epidérmicos. Todos os AGV induziram aumento proporcionalmente maior no peso do ruminorretículo que no peso do omaso, sendo o butirato aparentemente mais estimulador da massa do estômago aglandular. Embora o butirato tenha sido mais estimulador da secreção de insulina, os AGV foram incapazes de induzir ganho nas dimensões papilares. Os AGV aumentaram a proliferação celular nos epitélios do rúmen e do perioplum traseiro, contrariamente ao efeito sobre o plano nasolabial e a epicera. Os efeitos dos AGV sobre a morfologia da mucosa ruminal e de outros tecidos queratinizados sugerem que danos morfológicos no rúmen e cascos podem ter causa comum. Biópsias tegumentares podem ter utilidade como indicadores de alterações morfológicas da mucosa ruminal.

The effect of butyrate, propionate, and lactate on ruminal wall, epidermis of nasolabial surface, perioplum, and epicera of 17 neonatal calves was evaluated. The experiment also aimed to validate the procedure and interpretation of tegument biopsies as indicators of ruminal mucosa alterations. Serum insulin was sampled on the 22nd day from the beginning of treatments, at 0, 90, 180, and 360 minutes after the morning infusion. After slaughtering, samples were collected from ruminal wall, nasolabial surface, epicera, and perioplum from face and hindquarters. All volatile fatty acids (VFA) induced greater increase in ruminal-reticulum proportionate weight than in omasum. Butyrate was a greater stimulator of non-glandular stomach growth. Although butyrate stimulated more insulin secretion, this VFA was not capable to induced gain on papillae area or height. The effect of nasolabial surface VFA infusion was the opposite to that observed in the rumen. VFA increased hind perioplum mitotic index, contrary to its effect on the nasolabial surface and epicera. VFA effects on ruminal mucosa morphology and on other keratinized tissues suggest that morphological damage on hoof and ruminal epithelium may have a common cause. Tegumentary biopsies may be useful as indicators of morphological alterations of ruminal mucosa.

Alterações morfológicas induzidas por butirato, propionato e lactato sobre a mucosa ruminal e epiderme de bezerros: II. Aspectos ultra-estruturais / Lactate, propionate, and butyrate induced morphological alterations on calf ruminal mucosa and epidermis: II. Ultra-structurals aspects

Avaliou-se o efeito de ácidos graxos voláteis (AGV) sobre a integridade do epitélio no rúmen, no plano nasolabial, na epicera e no perioplum traseiro e dianteiro de bezerros e validou-se a feitura de biópsias tegumentares como indicadores de alterações morfológicas da mucosa ruminal. Dezessete bezerros, com sonda no rúmen, receberam infusões intra-ruminais de AGV ou salina, durante 37 dias. Aos 89 dias de vida, após o abate, foram colhidas amostras dos tecidos. Os AGV aumentaram a área de epitélio total e a área de células metabolicamente ativas no epitélio ruminal, embora o butirato não tenha induzido ao desenvolvimento papilar. A área de epitélio não queratinizado no plano nasolabial foi reduzida pela infusão de AGV. Butirato e lactato foram mais indutores de alterações patológicas no epitélio ruminal. Não foram observadas lesões histológicas nos epitélios do plano nasolabial, da epicera e do perioplum, mostrando que essas são conseqüências do efeito direto dos AGV sobre o epitélio ruminal. Os efeitos indireto e direto dos AGV sobre a morfologia dos tecidos epiteliais queratinizados não foram iguais. Biópsias tegumentares podem ter utilidade como indicadores de alterações morfológicas da mucosa ruminal.

The effect of volatile fatty acids (VFA) on rumen wall, epidermis of nasolabial surface, perioplum, and epicera of calves was evaluated. The experiment also aimed to validate the procedure of tegument biopsies as indicators of ruminal mucosa alterations. Seventeen neonatal calves with foley catheters received intraruminal infusions of VFA or saline, during 37 days. At 89-day-old, the animals were slaughtered and tissue samples were collected from rumen, nasolabial surface, epicera, and perioplum from face and hindquarters. VFA infusion increased total epithelium area and metabolically active ruminal cell area; although butirate did not induce the papilar development. The effect of nasolabial surface VFA infusion was the opposite to that observed in the rumen. No histological lesion was observed on nasolabial surface, epicera, and perioplum, demonstrating that these are consequences of VFA direct effect on ruminal epithelium. Butyrate and lactate induced more alterations on the ruminal epithelium. Indirect and direct VFA effects on keratinized epithelium tissues morphology were not identical. Tegumentary biopsies may be useful as indicators of morphological alterations of ruminal mucosa.

Produção de ácidos graxos voláteis e contagem de protozoários ruminais em bovinos suplementados com gordura / Volatile fatty acids production and counting of protozoa ruminate in bovine supplemented with fat

Os efeitos da utilização de sebo (SEBO) sobre contagem de protozoários ruminais e produção de ácidos graxos voláteis foram estudados em experimento em Quadrado Latino 3 x 3, utilizando-se 6 fêmeas bovinas (480 kg de P.V.) dotadas de cânulas ruminais, para avaliar três dietas, sem ou com 3 e 6% de sebo (SEBO). As coletas de líquido ruminal foram feitas no 21o dia de cada subperíodo experimental às 0, 1, 2, 3, 4, 6, e 8 horas após a 1a refeição. Houve redução dos protozoários totais, redução do conteúdo de ácidos graxos totais e mudança no padrão de fermentação com aumento na proporção de ácido propiônico e redução de ácido butírico nas dietas com 6% de sebo (SEBO) (p<0,05).

Effects of tallow (TALLOW) supplementation on counting of protozoa ruminate and production of volatile fatty acids were studied in a Latin Square (3 x 3) design, with six canulated heifers (480 kg body weight), to evaluate three diets, without or with 3 and 6% of tallow (TALLOW). Ruminal liquid collections were made at the twentieth first day of each experimental subperiod at 0, 1, 2, 3, 4, 6, and 8 hours after first meal. There was reduction significantly of the total of protozoa in the rumen content and change in the fermentation with increase in the molar percentage of propionate and reduction in the percentage molar of butyrate in the level of 6% of tallow (TALLOW) (p <0,05).

Solids separation coupled with batch-aeration treatment for odor control from liquid swine manure.

Previous studies on solids/liquid (S-L) separation for odor control from swine manure indicated that the practice might not technically be feasible because of the complexity of removing the fine particles, which are usually the major source of the odor problems. This study coupled S-L separation by sedimentation with an aeration treatment to quickly break down the fine as well as dissolved solids. Results showed that S-L separation of manure prior to aeration, at the same level of aeration, took only 1.5 days compared to 3 days needed for the control, to bring down volatile fatty acids (VFAs) to the "threshold of unacceptable level". In addition, it took 2.3 and 5 aeration-days for VFAs to reach the "acceptable level" for the separated liquid manure and the control, respectively. Results also showed that within the three weeks of post-aeration storage, the VFAs in the separated liquid manure consistently stayed 13.5 folds below the acceptable level. In the unseparated manure, the VFAs gradually increased upwards from 2.2 folds below acceptable level achieved at the end of aeration treatment, to 1.38 folds below the acceptable level at the end of the third week of storage and looked poised to definitely rise above the acceptable level in a matter of days. A strong relationship (R=0.99) between pH and the VFAs in the manure suggested that; degradation of VFAs rendered manure more basic as shown by the increase in pH. After only three days of aeration, the oxidation reduction potential (ORP) in the separated liquid manure stabilized at a much higher level of -15 mV, while the ORP in unseparated manure stabilized at a much lower level of -200 mV. The S-L separation treatment thus significantly improves the oxygen transfer efficiency, which in turn significantly reduces the aeration power needed to maintain adequate ORP if prolonged aeration is desired.

Effects of hydrochloric, acetic, butyric, and propionic acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses.

OBJECTIVE: To identify the pathogenesis of gastric ulcers by comparing injury to the nonglandular gastric mucosa of horses caused by hydrochloric acid (HCl) or volatile fatty acids (VFAs). SAMPLE POPULATION: Gastric tissues from 30 horses. PROCEDURE: Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance calculated for tissues after addition of HCl and VFAs to normal Ringer's solution (NRS). Tissues were examined histologically. RESULTS: Mucosa exposed to HCl in NRS (pH, 1.5) had a significant decrease in Isc, compared with Isc for mucosa exposed to NRS at pH 4.0 or 7.0. Also, exposure to 60mM acetic, propionic, and butyric acids (pH, 4.0 or 1.5) caused an immediate significant decrease in Isc. Recovery of sodium transport was detected only in samples exposed to acetic acid at pH 4.0. Recovery of sodium transport was not seen in other mucosal samples exposed to VFAs at pH < or = 4.0. CONCLUSIONS AND CLINICAL RELEVANCE: Acetic, butyric, and propionic acids and, to a lesser extent, HCl caused decreases in mucosal barrier function of the nonglandular portion of the equine stomach. Because of their lipid solubility at pH < or = 4.0, undissociated VFAs penetrate cells in the nonglandular gastric mucosa, which causes acidification of cellular contents, inhibition of sodium transport, and cellular swelling. Results indicate that HCl alone or in combination with VFAs at gastric pH < or = 4.0 may be important in the pathogenesis of gastric ulcers in the nonglandular portion of the stomach of horses.

Effects of hydrochloric, valeric, and other volatile fatty acids on pathogenesis of ulcers in the nonglandular portion of the stomach of horses.

OBJECTIVE: To identify in vitro effects of hydrochloric acid, valeric acid, and other volatile fatty acids (VFAs) on the pathogenesis of ulcers in the nonglandular portion of the equine stomach. SAMPLE POPULATION: Gastric tissues from 13 adult horses. PROCEDURE: Nonglandular gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference were measured and electrical resistance and conductance calculated after tissues were bathed in normal Ringer's solution (NRS) or NRS and hydrochloric, valeric, acetic, propionic, and butyric acids. Treated tissues were examined histologically. RESULTS: Incubation in 60mM valeric acid at pH < or = 7.0 abruptly and irreversibly abolished Isc, which was followed by a slower decrease in resistance and an increase in conductance. Incubation in 60mM acetic, propionic, and butyric acids and, to a lesser extent, hydrochloric acid at pH < or = 7.0 significantly decreased Isc, which was followed by an increase in resistance and a decrease in conductance. CONCLUSIONS AND CLINICAL RELEVANCE: Incubation in valeric acid at pH < or = 7.0 caused a dramatic decrease in mucosal barrier function in the nonglandular portion of the stomach. Changes in barrier function attributable to exposure to valeric acid were associated with histopathologic evidence of cellular swelling in all layers of the nonglandular mucosa. Because of its high lipid solubility, valeric acid penetrates the nonglandular gastric mucosa, resulting in inhibition of sodium transport and cellular swelling. Valeric acid and other VFAs in gastric contents may contribute to the pathogenesis of ulcers in the nonglandular portion of the stomach of horses.