Upregulation of L-type calcium channels in colonic inhibitory motoneurons of P/Q-type calcium channel-deficient mice
Enteric inhibitory motoneurons use nitric oxide and a purine neurotransmitter to relax gastrointestinal smooth muscle. Enteric P/Q-type Ca2+ channels contribute to excitatory neuromuscular transmission; their contribution to inhibitory transmission is less clear. We used the colon from tottering mice (tg/tg, loss of function mutation in the α1A pore-forming subunit of P/Q-type Ca2+ channels) to test the hypothesis that P/Q-type Ca2+ channels contribute to inhibitory neuromuscular transmission and colonic propulsive motility. Fecal pellet output in vivo and the colonic migrating motor complex (ex vivo) were measured. ...
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Rodriguez-Tapia, E., Perez-Medina, A., Bian, X., Galligan, J. J. Tags: NEUROGASTROENTEROLOGY AND MOTILITY Source Type: research

Aberrant fecal flora observed in guinea pigs with pressure overload is mitigated in animals receiving vagus nerve stimulation therapy
Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. Stimulation of the vagus nerve, which innervates the heart and abdominal organs, is proving to be an effective therapeutic in heart failure. We hypothesized that cervical vagus nerve stimulation (VNS) could alter fecal flora and prevent aberrations observed in fecal samples from heart failure animals. To determine whether microbial abundances were altered by pressure overload (PO), leading to heart failure and VNS therapy, a VNS pulse generator was implanted with a stimulus lead on either the left or right vagu...
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Phillips Campbell, R. B., Duffourc, M. M., Schoborg, R. V., Xu, Y., Liu, X., KenKnight, B. H., Beaumont, E. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Anti-inflammatory effects of Bifidobacterium longum subsp infantis secretions on fetal human enterocytes are mediated by TLR-4 receptors
This study suggests that PCM may use TLR-4 through IRAK-2 and via AP-1 to prevent IL-1β-induced IL-6 induction in immature enterocytes. Based on these observations, the combined use of probiotics and anti-TLR-4 therapy to prevent NEC may not be a good strategy. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Meng, D., Zhu, W., Ganguli, K., Shi, H. N., Walker, W. A. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Bacterial nutrient foraging in a mouse model of enteral nutrient deprivation: insight into the gut origin of sepsis
This study examined how metabolomic changes within the small bowel support an altered microbial community in enterally deprived mice. C57BL/6 mice were given TPN or enteral chow. Metabolomic analysis of jejunal contents was performed by liquid chromatography/mass spectrometry (LC/MS). In some experiments, leucine in TPN was partly substituted with [13C]leucine. Additionally, jejunal contents from TPN-dependent and enterally fed mice were gavaged into germ-free mice to reveal whether the TPN phenotype was transferrable. Small bowel contents of TPN mice maintained an amino acid composition similar to that of the TPN solution...
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Ralls, M. W., Demehri, F. R., Feng, Y., Raskind, S., Ruan, C., Schintlmeister, A., Loy, A., Hanson, B., Berry, D., Burant, C. F., Teitelbaum, D. H. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Statins improve NASH via inhibition of RhoA and Ras
Nonalcoholic steatohepatitis (NASH), especially as part of the metabolic syndrome (MS), is an increasing burden in Western countries. Statins are already used in MS and seem to be beneficial in liver diseases. The aim of this study was to investigate the molecular mechanisms underlying pleiotropic effects on small GTPases of statins in NASH. NASH within MS was induced in 12-wk-old apoE–/– mice after 7 wk of Western diet (NASH mice). Small GTPases were inhibited by activated simvastatin (SMV), NSC23766 (NSC), or Clostridium sordellii lethal toxin (LT) by using subcutaneous osmotic minipumps. Hepatic steatosis, i...
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Schierwagen, R., Maybüchen, L., Hittatiya, K., Klein, S., Uschner, F. E., Braga, T. T., Franklin, B. S., Nickenig, G., Strassburg, C. P., Plat, J., Sauerbruch, T., Latz, E., Lütjohann, D., Zimmer, S., Trebicka, J. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research

Deficiency of stearoyl-CoA desaturase-1 aggravates colitogenic potential of adoptively transferred effector T cells
Stearoyl-CoA desaturase-1 (SCD1) is a lipogenic enzyme involved in the de novo biosynthesis of oleate (C18:1, n9), a major fatty acid in the phospholipids of lipid bilayers of cell membranes. Accordingly, Scd1KO mice display substantially reduced oleate in cell membranes. An altered SCD1 level was observed during intestinal inflammation; however, its role in modulating inflammatory bowel disease remains elusive. Herein, we investigated the colitogenic capacity of Scd1KO effector T cells by employing the adoptive T-cell transfer colitis model. Splenic effector T cells (CD4+CD25–) from age- and sex-matched wild-type (W...
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Yeoh, B. S., Saha, P., Singh, V., Xiao, X., Ying, Y., Vanamala, J. K., Kennett, M. J., Harvatine, K. J., Joe, B., Vijay-Kumar, M. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research

Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model
Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carci...
Source: AJP: Gastrointestinal and Liver Physiology - October 6, 2016 Category: Gastroenterology Authors: Velazquez, K. T., Enos, R. T., Carson, M. S., Cranford, T. L., Bader, J. E., Chatzistamou, I., Singh, U. P., Nagarkatti, P. S., Nagarkatti, M., Davis, J. M., Carson, J. A., Murphy, E. A. Tags: STEM CELLS, TISSUE ENGINEERING, DEVELOPMENT, AND CANCER Source Type: research

Anti-TNF{alpha} alters the natural history of experimental Crohn's disease in rats when begun early, but not late, in disease
Anti-TNFα therapy decreases inflammation in Crohn's disease (CD). However, its ability to decrease fibrosis and alter the natural history of CD is not established. Anti-TNF-α prevents inflammation and fibrosis in the peptidoglycan-polysaccharide (PG-PS) model of CD. Here we studied anti-TNF-α in a treatment paradigm. PG-PS or human serum albumin (HSA; control) was injected into bowel wall of anesthetized Lewis rats at laparotomy. Mouse anti-mouse TNF-α or vehicle treatment was begun day (d)1, d7, or d14 postlaparotomy. Rats were euthanized d21-23. Gross abdominal and histologic findings were scored....
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Schmiedlin-Ren, P., Reingold, L. J., Broxson, C. S., Rittershaus, A. C., Brudi, J. S., Adler, J., Owens, S. R., Zimmermann, E. M. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research

Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells
In conclusion, our data support the concept that increased local glucose and insulin concentrations associated with obesity and T2DM promote PaSC growth and fibrosing responses. (Source: AJP: Gastrointestinal and Liver Physiology)
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Yang, J., Waldron, R. T., Su, H.-Y., Moro, A., Chang, H.-H., Eibl, G., Ferreri, K., Kandeel, F. R., Lugea, A., Li, L., Pandol, S. J. Tags: PANCREATIC PHYSIOLOGY/PATHOPHYSIOLOGY Source Type: research

Dysregulation of redox pathways in liver fibrosis
Reactive oxygen species are implicated in physiological signaling and cell fate decisions. In chronic liver diseases persistent and increased production of oxidative radicals drives a fibrogenic response that is a common feature of disease progression. Despite our understanding the biology of the main prooxidant enzymes, their targets, and antioxidant mechanisms in the liver, there is still lack of knowledge concerning their precise role in the pathogenesis of fibrosis. This review will examine the role of physiological redox signaling in the liver, provide an overview on recent advances in prooxidant and antioxidant pathw...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Torok, N. J. Tags: MINIREVIEW Source Type: research

Endocannabinoids in the gastrointestinal tract
The endocannabinoid system mainly consists of endogenously produced cannabinoids (endocannabinoids) and two G protein-coupled receptors (GPCRs), cannabinoid receptors 1 and 2 (CB1 and CB2). This system also includes enzymes responsible for the synthesis and degradation of endocannabinoids and molecules required for the uptake and transport of endocannabinoids. In addition, endocannabinoid-related lipid mediators and other putative endocannabinoid receptors, such as transient receptor potential channels and other GPCRs, have been identified. Accumulating evidence indicates that the endocannabinoid system is a key modulator ...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Lee, Y., Jo, J., Chung, H. Y., Pothoulakis, C., Im, E. Tags: REVIEWS Source Type: research

Monosodium glutamate inhibits the lymphatic transport of lipids in the rat
It is not well understood how monosodium glutamate (MSG) affects gastrointestinal physiology, especially regarding the absorption and the subsequent transport of dietary lipids into lymph. Thus far, there is little information about how the ingestion of MSG affects the lipid lipolysis, uptake, intracellular esterification, and formation and secretion of chylomicrons. Using lymph fistula rats treated with the infusion of a 2% MSG solution before a continuous infusion of triglyceride, we show that MSG causes a significant decrease in both triglyceride and cholesterol secretion into lymph. Intriguingly, the diminished lymphat...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Kohan, A. B., Yang, Q., Xu, M., Lee, D., Tso, P. Tags: NUTRIENT SENSING, NUTRITION, AND METABOLISM Source Type: research

Soluble bioactive microbial mediators regulate proteasomal degradation and autophagy to protect against inflammation-induced stress
In this study, we examined soluble factors derived from Bifidobacterium breve and their impact on the two major protein degradation systems within intestinal epithelial cells, proteasomes and autophagy. Conditioned media from gastrointestinal Gram-positive, but not Gram-negative, bacteria activated autophagy and increased expression of the autophagy proteins Atg5 and Atg7 along with the stress response protein heat shock protein 27. Specific examination of media conditioned by the Gram-positive bacterium Bifidobacterium breve (Bb-CM) showed that this microbe produces small molecules (<3 kDa) that increase expression of ...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Inaba, Y., Ueno, N., Numata, M., Zhu, X., Messer, J. S., Boone, D. L., Fujiya, M., Kohgo, Y., Musch, M. W., Chang, E. B. Tags: MICROBIOME AND HOST INTERACTIONS Source Type: research

Dual effects of a high-protein diet on DSS-treated mice during colitis resolution phase
In this study, we fed DSS-treated mice with either a normoproteic (NP) or a high-protein (HP) isocaloric diet from the beginning of the 5-day dextran sulfate sodium (DSS) treatment to 14 days later. Measurements of colitis indicators (colon weight:length ratio, myeloperoxidase activity, cytokine expressions) showed a similar level of colonic inflammation in both DSS groups during the colitis induction phase. However, during the colitis resolution phase, inflammation intensity was higher in the DSS-HP group than in the DSS-NP group as evidenced by higher inflammatory score and body weight loss. This coincided with a higher ...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Lan, A., Blais, A., Coelho, D., Capron, J., Maarouf, M., Benamouzig, R., Lancha, A. H., Walker, F., Tome, D., Blachier, F. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research

Probiotic Saccharomyces boulardii CNCM I-745 prevents outbreak-associated Clostridium difficile-associated cecal inflammation in hamsters
C. difficile infection (CDI) is a common debilitating nosocomial infection associated with high mortality. Several CDI outbreaks have been attributed to ribotypes 027, 017, and 078. Clinical and experimental evidence indicates that the nonpathogenic yeast Saccharomyces boulardii CNCM I-745 (S.b) is effective for the prevention of CDI. However, there is no current evidence suggesting this probiotic can protect from CDI caused by outbreak-associated strains. We used established hamster models infected with outbreak-associated C. difficile strains to determine whether oral administration of live or heat-inactivated S.b can pr...
Source: AJP: Gastrointestinal and Liver Physiology - September 30, 2016 Category: Gastroenterology Authors: Koon, H. W., Su, B., Xu, C., Mussatto, C. C., Tran, D. H.-N., Lee, E. C., Ortiz, C., Wang, J., Lee, J. E., Ho, S., Chen, X., Kelly, C. P., Pothoulakis, C. Tags: INFLAMMATION, IMMUNITY, FIBROSIS, AND INFECTION Source Type: research