Excessive Apoptosis in Ulcerative Colitis: Crosstalk Between Apoptosis, ROS, ER Stress, and Intestinal Homeostasis

Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium and destruction of the intestinal homeostasis, which has caused a huge social and economic burden on the health system all over the world. Its pathogenesis is multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, and dysregulated immune response. Thus far, although immune cells have become the focus of most research, it is increasingly clear that intestinal epithelial cells play an important role in the pathogenesis and progression of UC. Notably, apoptosis is a vital catabolic process in cells, which is crucial to maintain the stability of intestinal environment and regulate intestinal ecology. In this review, the mechanism of apoptosis induced by reactive oxygen species and endoplasmic reticulum stress, as well as excessive apoptosis in intestinal epithelial dysfunction and gut microbiology imbalance are systematically and comprehensively summarized. Further understanding the role of apoptosis in the pathogenesis of UC may provide a novel strategy for its therapy in clinical practices and the development of new drugs.

514 Late-Breaking: Effects of Feeding a High Canola Meal-containing Diet and Multi-carbohydrase Supplementation on Growth Performance and Intestinal Ecology of Piglets

The objective was to investigate the effects of a high canola meal-containing diet and multi-carbohydrase supplementation on growth performance and intestinal pH, short-chain fatty acid (SCFA) profile, and microbiome in weaned piglets. Twenty-four piglets (7.46 ± 0.23 kg BW) were individually assigned to 1 of 3 diets in a completely randomized design. Diets were fed for 21 d: SB, corn and soybean meal-based diet; CM, 25% canola meal substituting soybean meal and adjusted to meet energy and nutrient requirements of piglets (NRC, 2012); and CM+E, CM supplemented with multi-carbohydrase (0.01%). Feed disappearance and BW were recorded weekly. On d 21, piglets were euthanized to assess digesta pH, SCFA profile, and gut microbiome. Data were analyzed using the MIXED procedure of SAS using the piglet as the experimental unit. There were no differences (P > 0.10) in growth performance and digesta pH. Piglets fed CM+E tended to (P = 0.051) or had significantly lower (P < 0.05) butyric acid in the cecum than piglets fed CM and SB, respectively. Piglets fed SB had higher (P < 0.05) isobutyric acid in the colon than piglets fed CM+E. Piglets fed SB and CM tended to have higher (P < 0.05) isovaleric acid in the colon than piglets fed CM+E. Piglets fed SB tended to have lower (P < 0.10) proportion of Bifidobacteria, and had lower (P < 0.05) Enterobacteriaceae, Enterococcus, and Lactobacillus than piglets fed CM. Piglets fed CM+E tended to have lower (P < 0.10) Bifidobacteria and higher Clostridium XIVa than piglets fed CM, and had lower (P < 0.05) Enterococcus, but higher (P < 0.05) Lactobacillus than piglets fed CM. In conclusion, feeding 25% of canola meal in substitution to soybean meal with or without multi-carbohydrase supplementation changed the intestinal environment by modifying SCFA profile and relative proportion of microbiome, but without affecting digesta pH or growth performance in nursery piglets.

Association between gut dysbiosis and chronic kidney disease: a narrative review of the literature

Chronic kidney disease (CKD) is a serious non-communicable disease that poses a significant burden on healthcare and society. It is essential to devise new strategies to better treat patients with CKD. Research has illustrated that gut dysbiosis, describing an abnormal intestinal ecology, is closely associated with CKD. In this narrative review, we summarized the evidence of their mutual relationship and discussed the potential treatment options to correct gut dysbiosis in patients with CKD. Gut dysbiosis significantly increases the risk of CKD, especially in the older population. Gut dysbiosis also plays a role in CKD complications, such as hypertension, cardiovascular events, and cognitive dysfunction. The relationship between gut dysbiosis and CKD is bidirectional, and CKD itself can lead to changes in gut microecology. The usual therapies for CKD can also increase the incidence of gut dysbiosis. Meanwhile, probiotics and antibiotics are generally used to correct gut dysbiosis. Further studies are required to elaborate the association between gut dysbiosis and CKD, and more treatment options should be explored to prevent CKD in patients with gut dysbiosis.

Rifaximin: unique selective antibiotic for the treatment of gastrointestinal diseases

The human gut microbiota has been a major focus of scientific research in recent years. Studies based on metagenomic methods have revealed the multifaceted abilities of gut microbes, from metabolic functions to immunomodulation, from antipathogenic activity to behavioral formation. Since the gut microbiota plays a crucial role in maintaining human health, more or less specific changes in the gut microbiota are associated with various gastrointestinal diseases. These data strongly support the use of gut microbiota modulators, such as antibiotics, prebiotics and probiotics, as the choice for almost all gastrointestinal disorders. The traditional use of antibiotics in clinical practice is to counteract local or systemic infections. It can be assumed that antibiotics have a detrimental effect on the intestinal ecology. However, this is not true for all antibiotics.Rifaximin is a non-systemic oral antibiotic derived from rifampin and is characterized by a broad spectrum of antibacterial activity against Gram-positive and negative, aerobic and anaerobic bacteria. Rifaximin was first approved in Italy in 1987 and then in many other countries of the world for the treatment of several gastrointestinal diseases. This review presents the pharmacology and pharmacodynamics of rifaximin, describing various actions beyond its antibacterial activity, such as altering virulence, preventing intestinal mucosal adhesion and bacterial translocation. Key studies on the different uses of rifaximin are also described. In addition, rifaximin has some anti-inflammatory effects with minimal impact on the overall composition of the gut microbiota. All of these properties make rifaximin a good candidate for the treatment of various gastrointestinal diseases.

Intestinal morphology and growth performance of the Indonesian indigenous crossbred chickens supplemented with formic acid and Saccharomyces cerevisiae

The study investigated gut ecology and morphology of the Indonesian indigenous crossbred chickens (IICC) supplemented with the combination of formic acid and Saccharomyces cerevisiae. Two hundreds day-old IICC were distributed to T0 (control diet), T1 (T0 + 0.2% formic acid), T2 (T0 + 0.3% S. cerevisiae), T3 (T0 + 0.2% formic acid and 0.3% S. cerevisiae). Excreta was collected at week 8, while intestinal ecology and morphology were determined at week 9. In duodenum, T3 chicks showed higher and wider (P<0.05) villi. The T2 and T3 chicks showed deeper (P<0.05) crypt than that of T0. The jejunal villi was higher (P<0.05) in T3 than in T0. The T3 chicks had deeper (P<0.05) crypt compared to other groups. In ileum, the villi height was lowest (P<0.05) in T0. The crypt was deeper (P<0.05) in T3 than in other. Crude protein digestibility coefficient was highest (P<0.05), while fecal protein was loswest (P<0.05) in T1 than in other groups. Compared to T0, the treated IICC showed higher (P<0.05) weight gain and feed intake with T3 had the highest gain and intake but gain:feed rasio was the lowest (P>0.05). IIn conclusion, the inclusion of formic acid and S. cerevisiae in diets improved intestinal ecology and morphology. The IICC chickens fed with formic acid and S. cerevisiae exhibited improved growth performance and nutrient digestibility.

Methionine dietary supplementation potentiates ionizing radiation-induced gastrointestinal syndrome

Methionine is an essential amino acid needed for a variety of processes in living organisms. Ionizing radiation depletes tissue methionine concentrations and leads to the loss of DNA methylation and decreased synthesis of glutathione. In this study, we aimed to investigate the effects of methionine dietary supplementation in CBA/CaJ mice after exposure to doses ranging from 3 to 8.5 Gy of 137Cs of total body irradiation. We report that mice fed a methionine-supplemented diet (MSD; 19.5 vs. 6.5 mg/kg in a methionine-adequate diet, MAD) developed acute radiation toxicity at doses as low as 3 Gy. Partial body irradiation performed with hindlimb shielding resulted in a 50% mortality rate in MSD-fed mice exposed to 8.5 Gy, suggesting prevalence of radiation-induced gastrointestinal syndrome in the development of acute radiation toxicity. Analysis of the intestinal microbiome demonstrated shifts in the gut ecology, observed along with the development of leaky gut syndrome and bacterial translocation into the liver. Normal gut physiology impairment was facilitated by alterations in the one-carbon metabolism pathway and was exhibited as decreases in circulating citrulline levels mirrored by decreased intestinal mucosal surface area and the number of surviving crypts. In conclusion, we demonstrate that a relevant excess of methionine dietary intake exacerbates the detrimental effects of exposure to ionizing radiation in the small intestine. NEW & NOTEWORTHY Methionine supplementation, instead of an anticipated health-promoting effect, sensitizes mice to gastrointestinal radiation syndrome. Mechanistically, excess of methionine negatively affects intestinal ecology, leading to a cascade of physiological, biochemical, and molecular alterations that impair normal gut response to a clinically relevant genotoxic stressor. These findings speak toward increasing the role of registered dietitians during cancer therapy and the necessity of a solid scientific background behind the sales of dietary supplements and claims regarding their benefits.

Effect of a Fermented Mixture of Papaya Leaf and Seed Meal on Production Traits and Intestinal Ecology of the Indonesian Indigenous Crossbred Chickens

The work investigated the impact of a fermented mixture of papaya leaf and seed meal (FERM) on production traits, biochemical indices, intestinal ecology and carcass proportion of the Indonesian indigenous crossbred chickens (ICC). A 300 day-old ICC were assigned to five groups and fed on starter (1–4 weeks) and finisher diets (5–8 weeks) containing corn, soybean (CONT) or diets containing 1% (FERM1), 2.5% (FERM25), 5% (FERM5) or 7.5% (FERM75) of FERM. On week 8, blood was collected from birds prior to slaughter. The increased levels of FERM linearly reduced (P < 0.05) feed conversion and feed cost per kg weight gain, and increased (P < 0.05) income over feed cost of chickens. The relative weight of proventriculus linearly reduced (P < 0.05) with the enhanced contents of dietary FERM. The haemoglobin, erythrocytes and haematocrit values linearly reduced (P < 0.05) as the proportions of FERM enhanced. The mean corpuscular hemoglobin (MCH) levels were greater (P < 0.05) in FERM1 and FERM25 than that in control. The number of heterophils was greater (P < 0.05) in FERM1 than that in FERM25 and FERM5, but was not distinct from CONT and FERM75. The increased levels of FERM linearly increased (P < 0.05) thrombocytes values. Feeding FERM at 2.5% resulted in higher (P < 0.05) high-density lipoprotein (HDL) to low-density lipoprotein (LDL) ratio than that of control and FERM1. FERM reduced (P < 0.05) serum content of alanine aminotransferase (ALT). FERM75 had higher (P < 0.05) level of creatinine than control, FERM1 and FERM25. In duodenum, the increased levels of FERM linearly (P < 0.05) increased crypt depth (CD). At 7.5%, FERM reduced (P < 0.05) CD and enhanced (P < 0.05) villus height (VH) to CD ratio in jejunum. In ileum, CD linearly elevated (P < 0.05) with the increased FERM, while feeding 2.5% FERM enhanced (P < 0.05) VH and VH to CD ratio. In conclusion, FERM was beneficial in improving economic performance, immune responses, physiological condition and intestinal morphology of ICC.

Effect of feeding fermented mixture of cassava pulp and Moringa oleifera leaf meal on immune responses, antioxidative status, biochemistry indices, and intestinal ecology of broilers

Aim: The study investigated the effect of feeding fermented mixture of cassava pulp and Moringa oleifera leaf meal (FCPMO) on the immune responses, antioxidative status, biochemical parameters, and intestinal ecology of broiler chickens. Materials and Methods: Four hundred Lohmann broiler chickens were distributed to four groups of diets including CONT (corn-soybean-based feed with no additive), BACI (corn-soybean-based diet supplemented with 0.1% zinc bacitracin), FERM (diet containing 20% FCPMO), and FERB (diet containing 20% FCPMO and added with 0.1% Bacillus subtilis). At days 4, 14, and 19, the chicks were vaccinated using commercial Newcastle disease-infectious bursal disease (ND-IBD), IBD, and ND vaccines, respectively. At day 35, blood was sampled and digesta was obtained from the ileum and caecum. Furthermore, the duodenal segment was obtained. Results: The BACI, FERM, and FERB groups had higher (p<0.05) serum superoxide dismutase activity than control. The malondialdehyde was lower (p=0.07) in BACI, FERM, and FERB than that in CONT. The BACI and FERM had lower (p<0.05) leukocytes and lymphocytes than CONT. The hemoglobin, erythrocytes, and hematocrit were lower (p<0.05) in BACI and FERM than those in CONT and FERB. Serum total triglyceride was lower (p<0.05) in FERM and FERB than that in CONT. The FERM and FERB had higher (p<0.05) albumin levels. Serum globulin level was lower (p<0.05) in FERB than that in BACI, but did not differ from that in CONT and FERM. The numbers of coliform, lactose-negative enterobacteria and enterobacteria were lower (p<0.05) in FERB than that in other treatment groups. Crypt depth (CD) was higher (p<0.05) in FERM, while the villi height to CD ratio was lower (p<0.05) in FERM than that in CONT and FERB. The treatments showed no effect (p>0.05) on cecal volatile fatty acids production. Conclusion: Feeding FCPMO improved immune responses, antioxidative status, and physiological conditions, but had less effect on the intestinal ecology of broilers.