Resveratrol Ameliorates Intestinal Damage Challenged With Deoxynivalenol Through Mitophagy in vitro and in vivo

Deoxynivalenol (DON) reduces growth performance and damage intestinal function, and resveratrol (RES) has positive effects on growth performance and intestinal function. The purpose of this study was to investigate the protective mechanism of RES in vitro and vivo challenged with DON. The results showed that dietary supplementation with DON significantly increase the mRNA expression levels of mitophagy- related genes, and protein level for PINK1, Parkin, Beclin-1, Lamp, Atg5, Map1lc, Bnip3, Fundc1, Bcl2l1 and SQSTMS1 (P < 0.05), while supplementation with both RES and DON decreased those indexes in the ileum. Besides DON significantly decreased protein level for Pyruvate Dehydrogenase, Cytochrome c, MFN1, OPA1, and PHB1 (P < 0.05), while supplementation with both RES and DON increased protein level for PHB1, SDHA, and VDAC in the ileum. Moreover, in vitro, we found that DON significantly decreased mitochondrial respiration (P < 0.05), while RES + DON increased the rate of spare respiratory capacity. Also, DON significantly decreased total NAD and ATP (P < 0.05), while RES + DON increased the total NAD and ATP. These results indicate that RES may ameliorates the intestinal damage challenged with deoxynivalenol through mitophagy in weaning piglets.

The transcription factor HIF-1α mediates plasticity of NKp46+ innate lymphoid cells in the gut

Gut innate lymphoid cells (ILCs) show remarkable phenotypic diversity, yet microenvironmental factors that drive this plasticity are incompletely understood. The balance between NKp46+, IL-22–producing, group 3 ILCs (ILC3s) and interferon (IFN)-γ–producing group 1 ILCs (ILC1s) contributes to gut homeostasis. The gut mucosa is characterized by physiological hypoxia, and adaptation to low oxygen is mediated by hypoxia-inducible transcription factors (HIFs). However, the impact of HIFs on ILC phenotype and gut homeostasis is not well understood. Mice lacking the HIF-1α isoform in NKp46+ ILCs show a decrease in IFN-γ–expressing, T-bet+, NKp46+ ILC1s and a concomitant increase in IL-22–expressing, RORγt+, NKp46+ ILC3s in the gut mucosa. Single-cell RNA sequencing revealed HIF-1α as a driver of ILC phenotypes, where HIF-1α promotes the ILC1 phenotype by direct up-regulation of T-bet. Loss of HIF-1α in NKp46+ cells prevents ILC3-to-ILC1 conversion, increases the expression of IL-22–inducible genes, and confers protection against intestinal damage. Taken together, our results suggest that HIF-1α shapes the ILC phenotype in the gut.

Superiority of Microencapsulated Essential Oils Compared With Common Essential Oils and Antibiotics: Effects on the Intestinal Health and Gut Microbiota of Weaning Piglet

Essential oils (EOs) have long been considered an alternative to antibiotics in the breeding industry. However, they are unstable and often present unpleasant odors, which hampers their application. Microencapsulation can protect the active gradients from oxidation and allow them to diffuse slowly in the gastrointestinal tract. The purpose of this study was to investigate the effect of microencapsulation technology on the biological function of EOs and the possibility of using microencapsulate EOs (MEEOs) as an alternative to antibiotics in weaning piglets. First, we prepared MEEOs and common EOs both containing 2% thymol, 5% carvacrol and 3% cinnamaldehyde (w/w/w). Then, a total of 48 weaning piglets were randomly allotted to six dietary treatments: (1) basal diet; (2) 75 mg/kg chlortetracycline; (3) 100 mg/kg common EOs; (4) 500 mg/kg common EOs; (5) 100 mg/kg MEEOs; and (6) 500 mg/kg MEEO. The trial lasted 28 days. The results showed that piglets in the 100 mg/kg MEEOs group had the lowest diarrhea index during days 15–28 (P < 0.05). In addition, 100 mg/kg MEEOs significantly alleviated intestinal oxidative stress and inflammation (P < 0.05), whereas 500 mg/kg common EOs caused intestinal oxidative stress (P < 0.05) and may lead to intestinal damage through activation of inflammatory cytokine response. MEEOs (100 mg/kg) significantly reduced the ratio of the relative abundance of potential pathogenic and beneficial bacteria in the cecum and colon (P < 0.05), thus contributing to the maintenance of intestinal health. On the other hand, chlortetracycline caused an increase in the ratio of the relative abundance of potential pathogenic and beneficial bacteria in the colon (P < 0.05), which could potentially have adverse effects on the intestine. The addition of a high dose of MEEOs may have adverse effects on the intestine and may lead to diarrhea by increasing the level of colonic acetic acid (P < 0.05). Collectively, the results suggest that microencapsulation technology significantly promotes the positive effect of EOs on the intestinal health of weaning piglets and reduces the adverse effect of EOs, and 100 mg/kg MEEOs are recommended as a health promoter in piglets during the weaning period.

Mechanism of Neonatal Intestinal Injury Induced by Hyperoxia Therapy

High concentration oxygen is widely used in the treatment of neonates, which has a significant effect on improving blood oxygen concentration in neonates with respiratory distress. The adverse effects of hyperoxia therapy on the lung, retina, and neurodevelopment of newborns have been extensively studied, but less attention has been paid to intestinal damage caused by hyperoxia therapy. In this review, we focus on the physical, immune, and microorganism barriers of the intestinal tract and discuss neonatal intestinal tract damage caused by hyperoxia therapy and analyze the molecular mechanism of intestinal damage caused by hyperoxia in combination with necrotizing enterocolitis.

Probiotics: relevant during the coronavirus (COVID-19) infection pandemic?

The review presents modern views on the role of probiotics in the treatment and prevention of complications of the novel coronavirus COVID-19 infection. This infection can be complicated, for example, by the development of diarrhea after the use of antibacterial drugs in case of secondary bacterial infection, extrapulmonary viral infections, viremia, and the so-called «cytokine storm». The emphasis has been placed on such potentially beneficial effects of probiotics as а prevention of antibioticassociated diarrhea, prevention of intestinal damage induced directly by viral replication, prevention of leaky gut syndrome and immunomodulation in case of coronavirus COVID-19 infection. It has been shown that the use of probiotics alongside antibiotic therapy significantly reduces the risk of developing antibiotic-associated diarrhea, including such a severe variant as pseudomembranous colitis. The use of a probiotic during a viral respiratory disease reduces the risk of a severe disease course due to the positive modulation of inflammation and direct antiviral effects. Selected data showed the positive effect of probiotics on the tight junction stability of the intestine, which potentially protects against viremia and the penetration of immunogenic molecules into the internal environment of the body. In order to address the challenges adequately, a probiotic should meet certain requirements in terms of product quality, safety, evidence of efficacy, composition and understanding of the strains. The article presents data on the successful use of a multi-strain immuno-probiotic as an example demonstrating the therapeutic potential of modern multi-strain probiotics as a nonspecific immunomodulatory agent for the prevention of acute respiratory diseases.

S-Methylcysteine Ameliorates the Intestinal Damage Induced by Eimeria tenella Infection via Targeting Oxidative Stress and Inflammatory Modulators

Avian coccidiosis is one of the major parasitic diseases in the poultry industry. The infection is caused by Eimeria species, and its treatment relies mainly on the administration of anticoccidial drugs, which can result in drug resistance and side effects. The recent trends in avian coccidiosis treatment is directed to the development of a new therapy using herbal compounds. S-Methylcysteine (SMC) is considered one of the organosulfur compounds in garlic that showed promising activity in the treatment of different pathological conditions via a wide range of anti-inflammatory and antioxidant mechanisms. In this study, the anticoccidial activity of SMC was investigated in Eimeria tenella-infected chickens compared to diclazuril as a widely used anticoccidial drug. In this regard, 14-day-old broilers were divided into six groups (n = 18). The first group (G1) was the healthy control group, while the second group (G2) was the non-infected SMC group treated at a dose of 50 mg/kg b.w. (high dose). Moreover, the third group (G3) was the positive control group (infected and non-treated). The fourth group (G4) was the infected group treated with SMC of 25 mg/kg b.w. (low dose), while the fifth group (G5) was the infected group treated with SMC of 50 mg/kg b.w. (high dose). Conversely, the sixth group (G6) was the diclazuril-treated group. The anticoccidial effects of SMC and diclazuril were evaluated by counting oocysts and recording the body weight gain, feed conversion ratio, clinical signs, lesions, and mortality rate. Interestingly, SMC showed potent anticoccidial activity, which was exemplified by reduction of oocyst count. Furthermore, the biochemical, antioxidant, and anti-inflammatory parameters in the cecal tissues were restored toward their control levels in G4, G5, and G6. Histopathological observation of cecal tissues was consistent with the aforementioned results revealing the ameliorative effect of SMC against E. tenella infection. This study concluded novel findings in relation to the anticoccidial role of SMC as a plant-based compound against the E. tenella-induced coccidiosis in broiler chickens combined with its antioxidative and anti-inflammatory properties. Further studies for exploring the mechanistic pathways involved in this activity and the potential benefits from its use in association with conventional anticoccidial drugs are warranted.

Effects of Replacement of Dietary Fishmeal by Cottonseed Protein Concentrate on Growth Performance, Liver Health, and Intestinal Histology of Largemouth Bass (Micropterus salmoides)

An 8-week feeding trial was conducted to explore the effects of replacement of dietary fishmeal by cottonseed protein concentrate (CPC) on growth performance, liver health, and intestine histology of largemouth bass. Four isoproteic and isolipidic diets were formulated to include 0, 111, 222, and 333 g/kg of CPC, corresponding to replace 0% (D1), 25% (D2), 50% (D3), and 75% (D4) of fishmeal. Two hundred and forty largemouth bass (15.11 ± 0.02 g) were randomly divided into four groups with three replicates per group. During the experiment, fish were fed to apparent satiation twice daily. Results indicated that CPC could replace up to 50% fishmeal in a diet for largemouth bass without significant adverse effects on growth performance. However, weight gain rate (WGR), specific growth rate (SGR), feed efficiency (FE), and condition factor (K) of the largemouth bass were significantly decreased when 75% of dietary fishmeal that was replaced by CPC. The whole body lipid content was increased with the increasing of dietary CPC levels. Oil red O staining results indicated that fish fed the D4 diet showed an aggravated fat deposition in the liver. Hepatocytes exhibited serious degeneration, volume shrinkage, and inflammatory cells infiltration in the D4 group. Intestinal villi appeared shorter and sparse with severe epithelial damage in the D4 group. The transcription levels of anti-inflammatory cytokines, such as transforming growth factor β (tgf-β), interleukin 10 (il-10), and interleukin 11 β (il-11β), were downregulated in the D4 group. The lipid metabolism-related genes carnitine palmitoyl transferase 1 (cpt1), peroxisome proliferator-activated receptor α (pparα), and target of rapamycin (TOR) pathway were also significantly downregulated in the D4 group. It was concluded that suitable replacement of fishmeal by less than 222 g CPC/kg diet had a positive effect on growth performance of fish, but an excessive substitution of 75% fishmeal by CPC would lead to the suppressed growth, liver inflammation, and intestinal damage of largemouth bass.

Clinical and pathogenetic features of intestinal lesions in patients with type 2 diabetes mellitus

Objective — to study the incidence and clinical and pathogenetic features of intestinal injury in patients with type 2 diabetes mellitus. Materials and methods. Examinations involved 138 patients with type 2 diabetes mellitus (DM 2), aged from 39 to 67 years (mean age 53 ± 5 years), including 82 women (59 %) and 56 men (41 %). In addition to general clinical methods, investigations included plasma levels of the transforming growth factor‑b1 (TGF‑b1) and vascular endothelial growth factor (VEGF), the hydrogen breath test with lactulose, endoscopic examination of the intestine with biopsy followed by staining with hematoxylin‑eosin, immunohistochemical determining of claudin‑1 and VEGF, and conduction of PAS‑reaction. Results. Diabetic enterocolopathy (DECP) was diagnosed in 72 (52.2 %) patients with DM 2. Clinical manifestations were nonspecific and similar to those of irritable bowel syndrome (IBS). It has been found that DECP correlates with the duration of the DM 2 course and was diagnosed more often in middle‑aged patients (52.1 ± 4.1 years). In patients with DECP, the increase in the proinflammatory cytokines TGF‑b1 and VEGF significantly exceeded those in IBS patients. Histologically the inflammatory cell infiltration in patients with DECP was more intense and diverse, there were signs of subatrophy of the glands with a relative decrease in the number of vacuoles in the goblet cells. The immunohistochemical study revealed that VEGF in the colon mucosa was visualized mainly in patients with DECP. Moreover, a tendency to a decrease in the claudin‑1 levels was established in these patients. Conclusions. Intestinal damage was revealed in 67.4 % of patients with type 2 diabetes mellitus, and DECP was diagnosed in more than half of patients. Diabetic enterocolopathy had nonspecific clinical symptoms, required differential diagnosis with IBS, and was not always accompanied with abdominal pain. The presence of DECP more often correlated with the bacterial overgrowth syndrome, and levels of proinflammatory cytokines in the blood plasma and intestinal mucosa of these patients was raised.