Large Intestinal Contents Research Articles

Exploring microbiota-gut-brain axis biomarkers linked to autism spectrum disorder in prenatally chlorpyrifos-exposed Fmr1 knock-out and wild-type male rats

Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1 mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing gilts.

Study objectives were to evaluate the effects of mitoquinol (MitoQ) on production parameters, gastrointestinal tract (GIT; stomach and small and large intestines) weight, and circulating leukocytes during a 24-h acute heat stress (HS) challenge. Crossbred gilts [n = 32; 49.1 ± 2.4kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCON), 2) TN and MitoQ (n = 8; TNMitoQ), 3) HS control (n = 8; HSCON), or 4) HS and MitoQ (n = 8; HSMitoQ). Pigs were moved into individual pens and allowed to acclimate for 6 d. The study consisted of 2 experimental periods (P). During P1 (2 d), all pigs remained in TN conditions (20.6 ± 1.5 °C) and were fed ad libitum. During P2 (24h), pigs were fed ad libitum and exposed to either TN or constant HS (37.3 ± 1.3 °C). Mitoquinol (40mg/d) was orally administered twice daily (0700 and 1800 hours) during P1 and P2. As expected, pigs exposed to HS had increased rectal temperature, skin temperature, and respiration rate (+1.5 °C, +8.7 °C, and +86 bpm, respectively; P < 0.01) compared to their TN counterparts. Compared to TN, HS pigs had decreased feed intake (67%; P < 0.01) and significant BW loss (+1.5 vs. -1.9kg, respectively; P < 0.01). Total GIT weight was decreased in HS relative to TN pigs (P < 0.01), and this was influenced by decreased luminal contents (2.43 vs. 3.26kg, respectively; P < 0.01) and reduced empty GIT mass (3.21 vs. 3.48kg, respectively; P = 0.03). Stomach contents remained similar between TN and HS pigs (P > 0.54) but tended to increase in MitoQ relative to CON pigs (0.90 vs. 0.63kg, respectively; P = 0.08). Stomach content as a percentage of the previous 24h feed intake was increased in HS compared to the TN controls (93% vs. 31%; P < 0.01). In contrast, small and large intestinal contents were decreased in HS compared to TN pigs (23% and 49%, respectively; P < 0.01). Liver weight decreased in HS relative to TN pigs (1.15 vs. 1.22kg, respectively; P = 0.02), and was decreased in MitoQ compared to CON pigs (1.13 vs. 1.24kg; P < 0.01). Circulating lymphocytes tended to be decreased in HS relative to TN pigs (16%; P = 0.07). In summary, acute HS increased all body temperature indices, negatively influenced animal performance, and differentially altered GIT motility as evidenced by decreased gastric emptying and increased intestinal transit. However, MitoQ supplementation did not appear to ameliorate these effects.

PSIII-10 Effects of Mitoquinol During an Acute Heat Stress in Growing Gilts

Abstract Objectives were to evaluate the effects of mitoquinol (MitoQ) on production parameters, gastrointestinal (GIT) contents, GIT mass, and circulating leukocytes during acute heat stress (HS). Crossbred gilts [49.1±2.4 kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 therapeutic-environmental treatments: 1) thermoneutral (TN) control (TNCON; n = 8), 2) TN and MitoQ (TNMitoQ; n = 8), 3) HS control (HSCON; n = 8), or 4) HS and MitoQ (HSMitoQ; n = 8). The study consisted of two experimental periods (P). During P1 (2 d) pigs were fed ad libitum and housed in TN conditions (20.6±1.5°C). During P2 (24 h) pigs were fed ad libitum and exposed to either TN or constant HS (37.3±1.3°C). In MitoQ fed pigs, MitoQ (20 mg) was administered twice daily (0700 and 1800 h; 40 mg/d) during both P1 and P2. Rectal temperature (TR), skin (TS), respiration rate (RR), and feed intake (FI) were recorded every 4 h during P2. Following P2, all pigs were euthanized, and organs were weighed. As expected, pigs exposed to HS had increased TR, TS, and RR (1.5°C, 8.7°C, and 86 bpm, respectively; P &amp;lt; 0.01) relative to TN. Compared with TN, HS pigs had decreased FI (67%; P &amp;lt; 0.01). Additionally, HS pigs lost BW compared with TN (-1.9 vs. +1.5 kg, respectively; P &amp;lt; 0.01). Despite consuming 67% less feed, stomach contents were similar in TN and HS pigs (P &amp;gt; 0.54), regardless of environment. Large and small intestine contents were decreased in HS pigs relative to TN (23 and 49%, respectively; P ≤ 0.01). Total GIT luminal contents (stomach, small and large intestines) were decreased in HS relative to TN pigs (2.43 vs. 3.26 kg; P = 0.01); however, MitoQ fed pigs tended to have increased GIT contents regardless of the environment (3.05 vs. 2.63 kg; P = 0.08). Total empty GIT and liver weights decreased in HS relative to TN pigs (3.21 vs. 3.48 and 1.16 vs. 1.22 kg, respectively; P ≤ 0.03). In addition, liver weight was decreased in MitoQ relative to CON pigs (1.13 vs. 1.24 kg; P = 0.01). Further, total GIT weight (tissue and contents) was decreased in HS relative to TN pigs (5.63 vs. 6.70 kg; P = 0.01). Environment nor therapeutic treatment affected circulating leukocytes (P &amp;gt; 0.16); however, HS pigs tended to have decreased lymphocytes relative to TN (16%; P = 0.07). Based upon the changes in GIT content, it appears HS decreases gastric emptying while increasing intestinal passage rate. Overall, acute HS increased body temperature indices, and decreased FI, GIT mass and BW; however, MitoQ administration did not appear to ameliorate these metrics.

Characterization of microbiota and secretory Ig-A in the domestic duck (Anas platyrhynchos) small and large intestine

Abstract. Susanti R, Utami NR, Yuniastuti A. 2023. Characterization of microbiota and secretory Ig-A in the domestic duck (Anas platyrhynchos)small and large intestine. Biodiversitas 24: 2458-2466. The Microbiome composition could affect the duck's intestines' microenvironment, which may shape the microstructure's anatomy, metabolism, and immune system. Therefore, this study aims to characterize the intestinal microbiome's abundance, diversity, and IgA distribution in ducks' intestines. This study took 15 healthy domestic ducks (Anas platyrhynchosLinnaeus, 1758) from an intensive duck farm in Central Java, Indonesia. Five grams of each small and large intestine content were collected aseptically for metagenomic analysis. Then, the intestine organs were taken for immunohistochemistry preparations to depict the IgA distribution. The results showed that the small intestine has a greater bacterial abundance community, with 18 phyla, while only 13 are found in the large intestine. Interestingly, three phyla: Firmicutes, Actinobacteria, and Bacteroidetes, were found dominantly in both organs. However, the comparison of Firmicutes and Bacteroidetes ratio was higher in the small intestine (2357.76) than large intestine (10.64). The IgA distribution in the small and large intestines showed intermediate staining intensity (score: 2.07-2.20) and a final Allred score of 5.0 (positive). Even though dysbiosis microbiome was present in intestines with dominant species Streptococcus and Enterococcus, it seems no significant IgA over secretion. Understanding duck's gut immune response is important because it is highly tolerant to the pathogens that make them play an important role as an environmental reservoir for pathogenic viruses and bacteria and may potentially comprehend future infectious disease outbreaks.

Fatal gastritis and enterocolitis due to concurrent Helicobacter pylori and Campylobacter jejuni infection in a captive cheetah (Acinonyxjubatus)

A 3.5-year-old female cheetah (Acinonyx jubatus) died after a 10-day history of anorexia, regurgitation and diarrhoea despite symptomatic therapy. At gross post-mortem examination, the stomach was blood-filled with mucosal thickening and multifocal ulcerations. The intestinal mucosa was thickened and reddened, and the intestinal lumen was filled with dark red to black pasty content. Gastric histological lesions were compatible with gastritis due to Helicobacter infection, which was confirmed by polymerase chain reaction. Histology of the intestines revealed a severe necrotizing neutrophilic enterocolitis with abundant intralesional curved to spiral bacteria, corresponding to Campylobacter jejuni, which were subsequently isolated from both small and large intestinal contents. No other intestinal pathogens were detected despite thorough investigations. These findings suggest that C. jejuni may have played an aetiological role in the enterocolitis. Such an association has not been previously reported in non-domestic felids.

Effects of hazelnut protein isolate-induced food allergy on the gut microenvironment in a BALB/c mouse model.

Hazelnuts are reported as among the nuts that cause severe allergic reactions. However, few systematic studies exist on the changes in the gut microenvironment following hazelnut allergy. This study focused on the effects of hazelnut allergy on the duodenum, jejunum, ileum and colon microenvironment in vivo. We established a hazelnut protein isolate (HPI)-allergic mouse model, which was distinguished by the visible allergy symptoms, dropped temperatures and enhanced allergic inflammatory factor levels in serum, such as HPI-specific immunoglobulin E (sIgE), sIgG2a, interleukin-4, histamine, mouse mast cell protease-1, TNF-α, monocyte chemotactic protein-1 and lipopolysaccharide. For HPI sensitized mice, aggravated mast cell degranulation, severe morphologic damage and inflammatory cell infiltration were observed in the duodenum, jejunum, ileum, and colon, while goblet cell numbers were reduced in the duodenum, jejunum and ileum. Secretory IgA of the jejunum and tight junctions of the duodenum and jejunum were decreased significantly after HPI sensitization. There was no remarkable difference in the pH values of small intestinal contents, but the pH values of colonic contents were elevated, which was due to the decreased short-chain fatty acids (mainly acetate, propionate and butyrate) in the colon. The antioxidant capacity of both large and small intestinal contents declined after HPI sensitization, as evidenced by the increased malondialdehyde and decreased superoxide dismutase activity. HPI sensitization induced gut microbiota dysbiosis with decreased α diversity and altered β diversity in colonic contents. Spearman correlation analysis indicated that the increased characteristic genera, namely Bacteroides, Lactobacillus, Alloprevotella, Erysipelatoclostridium, Parabacteroides, and Helicobacter, played potentially synergistic roles in promoting allergy and gut microenvironment dysregulation.

A New Gnotobiotic Pig Model of P[6] Human Rotavirus Infection and Disease for Preclinical Evaluation of Rotavirus Vaccines.

Human rotavirus (HRV) is a leading cause of gastroenteritis in children under 5 years of age. Licensed vaccines containing G1P[8] and G1-4P[8] strains are less efficacious against newly emerging P[6] strains, indicating an urgent need for better cross protective vaccines. Here, we report our development of a new gnotobiotic (Gn) pig model of P[6] HRV infection and disease as a tool for evaluating potential vaccine candidates. The Arg HRV (G4P[6]) strain was derived from a diarrheic human infant stool sample and determined to be free of other viruses by metagenomic sequencing. Neonatal Gn pigs were orally inoculated with the stool suspension containing 5.6 × 105 fluorescent focus units (FFU) of the virus. Small and large intestinal contents were collected at post inoculation day 2 or 3. The virus was passaged 6 times in neonatal Gn pigs to generate a large inoculum pool. Next, 33-34 day old Gn pigs were orally inoculated with 10-2, 103, 104, and 105 FFU of Arg HRV to determine the optimal challenge dose. All pigs developed clinical signs of infection, regardless of the inoculum dose. The optimal challenge dose was determined to be 105 FFU. This new Gn pig model is ready to be used to assess the protective efficacy of candidate monovalent and multivalent vaccines against P[6] HRV.

Effect of a diet rich in galactose or fructose, with or without fructooligosaccharides, on gut microbiota composition in rats.

Recent studies suggest that a diet rich in sugars significantly affects the gut microbiota. Adverse metabolic effects of sugars may partly be mediated by alterations of gut microbiota and gut health parameters, but experimental evidence is lacking. Therefore, we investigated the effects of high intake of fructose or galactose, with/without fructooligosaccharides (FOS), on gut microbiota composition in rats and explored the association between gut microbiota and low-grade systemic inflammation. Sprague–Dawley rats (n = 6/group) were fed the following isocaloric diets for 12 weeks (% of the dry weight of the sugars or FOS): (1) starch (control), (2) fructose (50%), (3) galactose (50%), (4) starch+FOS (15%) (FOS control), (5) fructose (50%)+FOS (15%), (6) galactose (50%)+FOS (15%), and (7) starch+olive (negative control). Microbiota composition in the large intestinal content was determined by sequencing amplicons from the 16S rRNA gene; 341F and 805R primers were used to generate amplicons from the V3 and V4 regions. Actinobacteria, Verrucomicrobia, Tenericutes, and Cyanobacteria composition differed between diets. Bifidobacterium was significantly higher in all diet groups where FOS was included. Modest associations between gut microbiota and metabolic factors as well as with gut permeability markers were observed, but no associations between gut microbiota and inflammation markers were observed. We found no coherent effect of galactose or fructose on gut microbiota composition. Added FOS increased Bifidobacterium but did not mitigate potential adverse metabolic effects induced by the sugars. However, gut microbiota composition was associated with several metabolic factors and gut permeability markers which warrant further investigations.

Establishment of a gnotobiotic pig model of Clostridioides difficile infection and disease

Clostridioides difficile (C. difficile) is a gram-positive, spore-forming, anaerobic bacterium known to be the most common cause of hospital-acquired and antibiotic-associated diarrhea. C. difficile infection rates are on the rise worldwide and treatment options are limited, indicating a clear need for novel therapeutics. Gnotobiotic piglets are an excellent model to reproduce the acute pseudomembranous colitis (PMC) caused by C. difficile due to their physiological similarities to humans and high susceptibility to infection. Here, we established a gnotobiotic pig model of C. difficile infection and disease using a hypervirulent strain. C. difficile-infected pigs displayed classic signs of C. difficile infection, including severe diarrhea and weight loss. Inoculated pigs had severe gross and microscopic intestinal lesions. C. difficile infection caused an increase in pro-inflammatory cytokines in samples of serum, large intestinal contents, and pleural effusion. C. difficile spores and toxins were detected in the feces of inoculated animals as tested by anaerobic culture and cytotoxicity assays. Successful establishment of this model is key for future work as therapeutics can be evaluated in an environment that accurately mimics what happens in humans. The model is especially suitable for evaluating potential prophylactics and therapeutics, including vaccines and passive immune strategies.

Local and Systemic Effects of Green Coffee Extract (Coffea canephora) in Animal Model of Colorectal Carcinogenesis

ObjectivesEvaluate the local and systemic effects of aqueous extract of green coffee (GCE) in colorectal carcinogenesis (CRC) induced in rats. MethodsAdult Wistar rats (n = 48) were divided into two groups (C and T, n = 24). Group T was induced to CRC with 1,2-dimethylhydrazine (55 mg/kg, subcutaneously, weekly) for 5 weeks, and during this period all animals received standard AIN93-M diet. From week 6 to 15, the animals were divided into 4 groups (n = 12): C (healthy control fed AIN93-M diet), T (CRC- induced, fed AIN93-M diet), CGC (healthy control, fed AIN93-M diet + GCE), TGC (CRC-induced, fed AIN93-M diet + GCE). At 10th week, the pre-neoplastic lesions were evaluated in 4 rats from each group. The remaining rats (n = 8) were feed their experimental diet until the 15th week. In the last week, 24 h-urine collection was performed for intestinal permeability analysis using lactulose (100 mg/kg) and mannitol (50 mg/kg) administration. Afterwards, blood samples were collected to the analyses of plasma cytokines (TNF-alpha, interleukins IL-6, 10 and 12) and total antioxidant capacity (TAC). Large intestine content was collected for pH and secretory immunoglobulin A (sIgA) analyses. The microscopic lesions were evaluated in the colorectal mucosa. ResultsTGC group had the highest aberrant crypt foci (ACF) count, 51% higher compared to the T group. Intestinal permeability was increased in the T group. There was no significant difference in the quantification of cytokines TNF-alpha, IL-6, 10 and 12. Both TGC and T showed high values of TAC. Intestinal pH was significantly higher in CGC group compared to TGC. There was no significant difference in the quantification of sIgA between groups. The reduction of malignant neoplastic changes was 42% and of benign changes was 66% and there was a reduction of 33.33% and 20% of hyperplasia and dysplasia, respectively, in TGC compared with T group. ConclusionsGCE was beneficial for intestinal permeability and controlled the development of neoplasms in the colorectal mucosa, without interfering with systemic inflammation, reinforcing that GCE reduces the risk of developing the CRC. Funding SourcesThis study was financed by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and FAPES (Fundação de Amparo à Pesquisa e Inovação do Espírito Santo), Brazil.

Bacterial and Fungal Adaptations in Cecum and Distal Colon of Piglets Fed With Dairy-Based Milk Formula in Comparison With Human Milk.

Exclusive breastfeeding is recommended to newborns during the first 6 months of life, whereas dairy-based infant formula is an alternative nutrition source offered to infants. Several studies demonstrated that breastfed infants have a different gut bacterial composition relative to formula-fed infants. In addition, animal models have shown that human milk (HM)–fed piglets had a distinct intestinal bacterial composition compared with milk formula (MF)–fed piglets. However, the gut fungal composition and the interactions with the bacterial community in breastfed compared with formula-fed infants remain to be investigated. In an attempt to evaluate such differences, we used an animal model to perform a shotgun metagenomics analysis on the cecal and distal colon contents of neonatal piglets fed with pasteurized HM or a dairy-based infant formula (MF) during the first 21 days of life. At postnatal day 21 (PND 21), a subset of piglets from each diet group (n = 11 per group) was euthanized. The remaining piglets in each group were weaned to a solid diet and euthanized at PND 51 (n = 13 per group). Large intestine contents (i.e., cecum and distal colon) were subjected to shotgun metagenomics analysis. The differential taxonomic composition of bacteria and fungi and the predicted functional gene profiling were evaluated. Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria are the most abundant bacterial phyla observed in piglets at PND 21 and PND 51. In the large intestine at PND 21 and PND 51, Proteobacteria phylum was significantly higher in MF-fed group, and species Burkholderiales bacterium of phyla was significantly higher in MF group relative to HM group. In addition, in HM group, several Lactobacillus spp. and Bacteroides spp. were higher relative to MF group in the large intestine at PND 21 and PND 51. Fungal genus Aspergillus was higher in MF, whereas Malassezia was lower relative to HM group. Persistent effects of the neonatal diets were observed at PND 51, where alpha- and beta-diversity differences were detected for bacterial and fungal species in the large intestine. Overall, our findings indicate that neonatal diet affects the large intestinal microbial community during the exclusive milk-feeding period, as well as after the introduction of the complementary food.

Cadmium exposure modulates the gut-liver axis in an Alzheimer\u2019s disease mouse model

The human Apolipoprotein E4 (ApoE4) variant is the strongest known genetic risk factor for Alzheimer’s disease (AD). Cadmium (Cd) has been shown to impair learning and memory at a greater extent in humanized ApoE4 knock-in (ApoE4-KI) mice as compared to ApoE3 (common allele)-KI mice. Here, we determined how cadmium interacts with ApoE4 gene variants to modify the gut-liver axis. Large intestinal content bacterial 16S rDNA sequencing, serum lipid metabolomics, and hepatic transcriptomics were analyzed in ApoE3- and ApoE4-KI mice orally exposed to vehicle, a low dose, or a high dose of Cd in drinking water. ApoE4-KI males had the most prominent changes in their gut microbiota, as well as a predicted down-regulation of many essential microbial pathways involved in nutrient and energy homeostasis. In the host liver, cadmium-exposed ApoE4-KI males had the most differentially regulated pathways; specifically, there was enrichment in several pathways involved in platelet activation and drug metabolism. In conclusion, Cd exposure profoundly modified the gut-liver axis in the most susceptible mouse strain to neurological damage namely the ApoE4-KI males, evidenced by an increase in microbial AD biomarkers, reduction in energy supply-related pathways in gut and blood, and an increase in hepatic pathways involved in inflammation and xenobiotic biotransformation.

Effect of Sustained Administration of Thymol on Its Bioaccessibility and Bioavailability in Rabbits.

Simple SummaryThe purpose of this study was to investigate the bioavailability and metabolic path of thymol, a major constituent of Thymus vulgaris L., in the rabbit organism. Oral bioavailability is a key parameter affecting the efficacy of substances, but it is not surprising that it does not correlate satisfactorily with efficacy. The main limitation factors are rate of absorption, metabolism, and excretion processes. In this work, the thymol metabolic path in the rabbit organism was determined for the first time after its sustained oral administration. We confirm intensive absorption of thymol from the gastrointestinal tract; our results point to metabolism and accumulation in kidney tissue and intensive metabolic and excretion processes in the liver. Some metabolic processes were present also after thymol withdrawal. Thymol as a lipophilic substance was found only in trace amounts in fat and muscle tissue as a consequence of its conversion into hydrophilic metabolite and greater elimination in the rabbit organism. This paper highlights the insufficient knowledge of modes of action of plant compounds in animal organisms.The objective of this study was the detection of thymol in rabbit plasma, tissues, large intestinal content, and faeces. Forty-eight rabbits were divided into control and experimental groups (thymol 250 mg/kg feed). Thymol was administered for 21 days and then withdrawn for 7 days. Concentration of thymol in the intestinal wall (IW) was significantly higher than in plasma (p < 0.05) and liver (p < 0.05); in the kidneys it was significantly higher than in plasma (p < 0.05) and liver (p < 0.05) during thymol addition. Thymol in IW was significantly higher than in plasma also after withdrawal (p < 0.01). Significant correlation (rs = −1.000, p < 0.01) between IW and plasma points to the intensive absorption of thymol from the intestine, while the correlation between plasma and liver (rs = 0.786, p < 0.05) indicates intensive biotransformation and excretion processes in liver. Significant correlation between liver and kidney (rs = 0.738, p < 0.05) confirms the intensive metabolism of thymol in the kidney. During the withdrawal period, thymol was detected above trace amounts only in faeces, and was significantly higher than in the colon during both periods (p < 0.01). Results show intensive biotransformation of thymol in the rabbit organism.

Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach.

The increase of multidrug-resistant (MDR) bacteria has renewed interest in old antibiotics, such as minocycline, that can be active against various MDR Gram-negative pathogens. The elimination of minocycline by both kidneys and liver makes it suitable for impaired renal function patients. However, the drawback is the possible elimination of a high amount of drug in the intestines, with potential impact on the digestive microbiota during treatment. This study aimed to predict the potential activity of minocycline against Enterobacterales in the gut after parenteral administration, by combining in vivo and in vitro studies. Total minocycline concentrations were determined by UPLC-UV in the plasma and intestinal content of piglets following intravenous administration. In parallel, the in vitro activity of minocycline was assessed against two Escherichia coli strains in sterilized intestinal contents, and compared to activity in a standard broth. We found that minocycline concentrations were 6–39 times higher in intestinal contents than plasma. Furthermore, minocycline was 5- to 245-fold less active in large intestine content than in a standard broth. Using this PK-PD approach, we propose a preclinical pig model describing the link between systemic and gut exposure to minocycline, and exploring its activity against intestinal Enterobacterales by taking into account the impact of intestinal contents.

Nicotinamide Ameliorates Dextran Sulfate Sodium-Induced Chronic Colitis in Mice through Its Anti-Inflammatory Properties and Modulates the Gut Microbiota.

Vitamin B (nicotinamide (NAM)), one of the most important nutritional components for humans, exerts anti-inflammatory activity. This study was aimed at investigating the effect of NAM on the gut microbiota and short-chain fatty acids (SCFAs) in mice with chronic colitis. Colitis was induced in C57BL/6 male mice by administration of 1.5% dextran sulfate sodium (DSS), and the mice were intraperitoneally injected with normal saline (NS) or NAM. NAM treatment ameliorated weight loss and changes in colon length, disease activity index (DAI) score, and histologic scores. Moreover, enzyme-linked immunosorbent assay (ELISA) analysis of LPL cells revealed that the level of interleukin- (IL-) 6, IL-12p70, IL-1β, tumor necrosis factor- (TNF-) α, interferon- (IFN-) γ, IL-21, and IL-17A was increased, while IL-10 was reduced, in the chronic colitis group compared to the control group, but the levels of all these factors were restored after NAM treatment. Then, 16S rRNA sequencing of the large intestinal content was performed, and analysis of alpha diversity and beta diversity showed that the richness of the gut microbiota was decreased in the DSS group compared to the control group and restored after NAM treatment. In addition, NAM modulated specific bacteria, including Odoribacter, Flexispira, and Bifidobacterium, in the NAM+chronic colitis group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that NAM treatment restored disruptions in the functions of the gut microbiota (replication and repair, cell motility) in mice with DSS-induced colitis. Furthermore, NAM also restored the reduction in valeric acid in mice with DSS-induced chronic colitis. Our results suggest that NAM treatment could alleviate DSS-induced chronic colitis in mice by inhibiting inflammation and regulating the composition and function of gut microbiota.

Early-life supplementation of grape polyphenol extract promotes polyphenol absorption and modulates the intestinal microbiota in association with the increase in mRNA expression of the key intestinal barrier genes.

Early-life nutritional supplementation can dramatically influence health status. Dietary polyphenols are a widespread group of phytochemicals with potential bioactive functions. However, how polyphenol intake during early life affects health status remains largely unknown. Mice aged 3- and 6-weeks were used to investigate how grape polyphenol extract (GPE) administration during early life altered polyphenol absorption, the intestinal microbiota, and the intestinal barrier. After a 2-week GPE supplementation, there were more diverse polyphenol metabolites in the plasma of 3-week-old mice than in the plasma of 6-week-old mice. Correspondingly, GPE supplementation increased the mRNA expression of genes related to polyphenol absorption in 3-week-old mice but not 6-week-old mice. Early-life GPE administration also stimulated the key genes of the small intestinal barrier in mice. Moreover, the key genes of the small intestinal barrier were positively associated with the genes related to polyphenol absorption in the small intestine of 3-week-old mice. In addition, fecal Akkermansia and Lactobacillus were increased, as evidenced by 16S rRNA gene sequencing. As a result, the acetate and butyrate production in the large intestinal content was enhanced, and the mRNA expression of the key genes involved in the large intestinal barrier was also increased. Thus, our study demonstrates that dietary polyphenol intake in early life induces improvements in polyphenol absorption, the intestinal microbiota, and the intestinal barrier, suggesting the importance of polyphenol-rich nutritional programming during early life on health status.

INQUISITION OF CARDIOPULMONARY AND KIDNEY LESIONS PRODUCED BY NATURAL PERACUTE AND ACUTE CLOSTRIDIUM TYPE D ENTEROTOXEMIA IN CHINKARA DEER

This study describes the clinical signs, postmortem lesions and histopathological findings in chinkara deer died during an outbreak of enterotoxaemia. The study included 7 chinkara deer. During the outbreak, 5 chinkara deer died without clinical signs while 2 chinkara deer showed clinical signs before death. Clinical signs including greenish watery diarrhea, chocolate colored urine, herding in a corner with head down, fever, anorexia and opisthotonos. After death of these 7 deer, necropsy performed and observed soft and swollen kidneys, straw color fluid in abdominal cavity, edematous and congested lungs, hydrothorax, hydropericardium, hemorrhages and ballooning of small and large intestine and watery contents in the small intestine. In per-acute cases multifocal petechial hemorrhages on jejunal mucosa and myocardium were frequently observed. The histologic changes were perivascular cuffing in lungs and proteinaceous fluid in alveoli, pulmonary edema and hemorrhagic enteritis. Disruption of renal tubular epithelial cells, necrosis and congestion observed in histopathological section of kidneys. Affected deer was treated with different drugs and supplements but unfortunately prognosis was death. Enterotoxaemia is more fatal in young deer than adult. On the basis of this study we found that enterotoxaemia clinical signs, postmortem lesions and histopathological changes in deer are same as other animals such as sheep and goats.

ВЛИЯНИЕ ОБЕЗЖИРЕННОГО КИСЛОМОЛОЧНОГО НАПИТКА, ПОЛУЧЕННОГО ПРИ СБРАЖИВАНИИ ШТАММАМИ LACTOBACILLUS FERMENTUM AG8 И LACTOBACILLUS PLANTARUM AG9, НА ПРОДУКТИВНЫЕ ПОКАЗАТЕЛИ КРЫС

In this work the influence of skimmed dairy product fermented by strains L. fermentum AG8 or L. plantarum AG9 on laboratory animals is investigated. Wistar rats were used as a model and fermented milk products were introduced into their diet. Laboratory Wistar rats were used as a model and fermented milk product was introduced into their diet. At the end of the experiment productivity, morphology of gastrointestinal organs, liver and kidneys, microbiological composition of the large intestine content were evaluated. The use of fermented milk product with lactobacilli in the diet increases the growth of weight of animals, does not adversely affect the digestive system, liver and kidneys. Introduction to the diet of this dairy product leads to a decrease in the number of yeast and coliform bacteria in the intestines of rats.

Динамика показателей перекисного окисления липидов в толстом кишечнике при экспериментальной болезни Крона в условиях применения ректальных суппозиториев с экстрактом корневищ куркумы длинной

Цель исследования - проведение сравнительного анализа влияния экстракта куркумы длинной и 5-аминосалициловой кислоты (5-АСК) в составе ректальных суппозиториев на клиническую картину и содержание продуктов перекисного окисления липидов (ПОЛ) в слизистой оболочке толстого кишечника при экспериментальной болезни Крона (БК). Методика. Эксперимент выполнен на 70 белых крысах-самцах Wistar. БК моделировали ректальным введением тринитробензосульфоновой кислоты. Ректальные суппозитории (массой 0,3 г каждая) начинали применять через 12 ч. Содержание 5-АСК в суппозиториях составляло 50 мг, 10% экстракта куркумы длинной оригинального состава 0,000075 г. На 3-и, 5-е и 7-е сут после моделирования БК оценивали клинический статус по модифицированной шкале Disease activity index и содержание продуктов ПОЛ в слизистой оболочке толстого кишечника. Результаты. В динамике БК в толстом кишечнике увеличивается содержание первичных, вторичных и конечных продуктов ПОЛ в гептановой и изопропанольной фазах; тяжесть клинических признаков (снижение массы тела, диарея, кровь в каловых массах) нарастает по мере увеличения содержания продуктов ПОЛ. Применение при БК ректальных суппозиториев с экстрактом куркумы снижает выраженность клинических симптомов, уменьшает содержание продуктов ПОЛ преимущественно в изопропанольной фазе липидного экстракта толстого кишечника; установлена корреляция индекса клинической активности БК с содержанием продуктов ПОЛ в толстом кишечнике. Заключение. Эффективность локального применения экстракта куркумы в составе ректальных суппозиториев сопоставима по эффективности с применением ректальных суппозиториев с 5-АСК по показателям индекса клинической активности и по содержанию продуктов ПОЛ в слизистой толстого кишечника. Aim. To compare effects of turmeric extract and 5-aminosalicylic acid (5-ASA) formulated into rectal suppositories on clinical symptoms and content of lipid peroxidation products (LPP) in the mucous membrane of the large intestine in experimental Crohn’s disease (CD). Methods: Experiments were performed on 70 Wistar male rats. CD was modeled by rectal administration of trinitrobenzenesulfonic acid; rectal suppositories (0.3 g each) were used every 12 h. The suppositories contained 5-ASA (50 mg) or 10% turmeric extract with an original composition (0.000075 g). On days 3, 5, and 7 of CD, the clinical status was evaluated with a modified Disease Activity Index scale, and LPP concentrations were measured in the large intestine mucosa. Results. In the course of CD in the colon, concentrations of primary, secondary, and final LPP in the heptane and isopropanol phases increased; severity of clinical signs (weight loss, diarrhea, blood in fecal masses) increased with increasing LPP concentrations. The use of rectal suppositories with turmeric extract alleviated severity of clinical symptoms and reduced LPP content primarily in the isopropanol phase of colon lipid extract. The index of CD clinical activity of CD was correlated with the large intestinal LPP content. Conclusion. Effectiveness of the local application of turmeric extract formulated into rectal suppositories was comparable with that of rectal suppositories with 5-ASA as determined by the Disease Activity Index and the LPP content in the large intestine.

Prevalence of Salmonella in green anoles (Anolis Carolinensis), an invasive alien species in Naha and Tomigusuku Cities, Okinawa Main Island, Japan.

Here, we investigated the prevalence of Salmonella enterica, with and without resistance to 17 common antimicrobial agents, in 706 green anoles (Anolis carolinensis) that were collected in Naha and Tomigusuku Cities, Okinawa Main Island, Japan, between 2009 and 2014. Salmonella strains, including S. enterica Weltevreden and Enteritidis serovars, were identified in the large intestinal content samples extracted from 15 (2.1%) of the analyzed green anoles. No antimicrobial resistance was detected. Thus, the present study demonstrates that although the prevalence of Salmonella and the risk of its transmission from the green anoles to humans or other animals on Okinawa Main Island are relatively low, the green anole population nevertheless represents a potential source of Salmonella infection that could affect human health in this region.