Pathogenesis Of Diarrhea Research Articles

Destruction of the brush border by Salmonella enterica sv. Typhimurium subverts resorption by polarized epithelial cells.

Salmonella enterica serovar Typhimurium is an invasive, facultative intracellular gastrointestinal pathogen that destroys the brush border of polarized epithelial cells (PEC). The brush border is critical for the functions of PEC because it resorbs nutrients from the intestinal lumen and builds a physical barrier to infecting pathogens. The manipuation of PEC during infection by Salmonella was investigated by live-cell imaging and ultrastructural analysed of the brush border. We demonstrate that the destruction of the brush border by Salmonella significantly reduces the resorption surface of PEC along with the abrogation of endocytosis at the apical side of PEC. Both these changes in the physiology of PEC were associated with the translocation of type III secretion system effector protein SopE. Additionally, the F-actin polymerization rate at the apical side of PEC was highly altered by SopE, indicating that reduced endocytosis observed in infected PEC is related to the manipulation of F-actin polymerization mediated by SopE and, to a lesser extent, by effectors SopE2 or SipA. We further observed that in the absence of SopE, Salmonella effaced microvilli and induced reticular F-actin by bacterial accumulation during prolonged infection periods. In contrast to strains translocating SopE, strains lacking SopE did not alter resorption by PEC. Finally, we observed that after engulfment of Salmonella, ezrin was lost from the apical side of PEC and found later in early endosomes containing Salmonella. Our observations suggest that the destruction of the brush border by Salmonella may contribute to the pathogenesis of diarrhea.

Diarrhea in COVID‑19: Causes and approaches to therapy

The article presents the results of a study of the frequency of diarrheal syndrome in patients with COVID‑19. The pathogenesis of diarrhea and its differences from other acute respiratory infections are considered in detail, including on a clinical example.Objective. To study the frequency of registration, features and results of pathogenetic therapy for diarrhea in patients with confirmed COVID‑19.Materials and methods. 286 case histories of male and female patients aged 18–96 years old who received outpatient treatment from June 2020 to February 2021 in connection with the confirmed diagnosis of COVID‑19 were analyzed.Results. Diarrhea was noted in 72 (25.0%) patients. In 4 (1.4%) patients, it was the only symptom of COVID‑19, in 15 (20.8%) – manifesting, followed by the addition and increase of catarrhal symptoms and manifestations of intoxication. In most cases (in 53 patients – 73.6%), diarrheal syndrome appeared simultaneously with other complaints or somewhat later.Conclusions. 1). According to the study, COVID‑19 in 25% of patients is accompanied by diarrhea, in most cases of a watery nature. 2). Different pathogenesis of diarrheal syndrome is possible in patients with COVID‑19. 3). The use of rehydration solutions with additional components, cytomucoprotective and probiotic therapy can reduce the period of diarrhea in patients with COVID‑19 to 1–3 days and prevents adverse effects.

The dysfunction in intestinal microorganisms and enzyme activity as significant contributors to diarrhea with kidney-yang deficiency syndrome.

To investigate the pathogenesis of diarrhea with kidney-yang deficiency syndrome by examining characteristic changes in intestinal microorganisms, enzyme activities, oxidative stress, and metabolism indices. Twenty mice were randomly and equally divided into control group (NC) and model group (NM). Mice in NM group received adenine suspension at a dosage of 50 mg/(kg⋅day) by gavage, 0.4 mL/time, once a day for 14 days, and Folium sennae decoction at a dosage of 10 g/(kg⋅day) by gavage, 0.4 mL/time, once a day for 7 days, starting on 8th day. Mice in NC group were administered an equivalent amount of sterile water by gavage once a day for 7 days, and twice a day from the 8th day. After modeling, assessments encompassed microbial culture, organ index calculation, microbial and enzyme activity detection, malondialdehyde (MDA) content determination, superoxide dismutase (SOD) activity, blood biochemical tests, and observation of kidney tissue pathological changes. The results showed that in NM group, a reduction in the number of Lactobacillus and Bifidobacteria was noted, accompanied by an increase in the number of bacteria and E. coli. Xylanase activity in the intestinal contents and mucosa, protease activity in the intestinal mucosa, and intestinal mucosa microbial activity were diminished. Conversely, the activities of amylase, sucrase, and lactase increased in intestinal mucosa. Additionally, there was an elevation in the level of MDA. Renal tubular dilatation and inflammatory cell infiltration were observed in the renal interstitium. These dysfunctions in intestinal microorganisms and enzyme activities suggest potential involvement in diarrhea with kidney-yang deficiency syndrome.

Postbiotic Preparation of Lacticaseibacillus rhamnosus GG against Diarrhea and Oxidative Stress Induced by Spike Protein of SARS-CoV-2 in Human Enterocytes.

The Spike protein of SARS-CoV-2 acts as an enterotoxin able to induce chloride secretion and production of reactive oxygen species (ROS), involved in diarrhea pathogenesis. L. rhamnosus GG (LGG) is recommended in pediatric acute gastroenteritis guidelines as a therapy independent of infectious etiology. We tested a postbiotic preparation of LGG (mLGG) in an in vitro model of COVID-associated diarrhea. Caco-2 cell monolayers mounted in Ussing chambers were exposed to Spike protein, and electrical parameters of secretory effect (Isc and TEER) were recorded in the Ussing chambers system. Oxidative stress was analyzed by measuring ROS production (DCFH-DA), GSH levels (DNTB), and lipid peroxidation (TBARS). Experiments were repeated after mLGG pretreatment of cells. The Isc increase induced by Spike was consistent with the secretory diarrhea pattern, which was dependent on oxidative stress defined by a 2-fold increase in ROS production and lipid peroxidation and variation in glutathione levels. mLGG pretreatment significantly reduced the secretory effect (p = 0.002) and oxidative stress, namely ROS (p < 0.001), lipid peroxidation (p < 0.001), and glutathione level changes (p < 0.001). LGG counteracts Spike-induced diarrhea by inhibiting the enterotoxic effect and oxidative stress. The LGG efficacy in the form of a postbiotic depends on metabolites secreted in the medium with antioxidant properties similar to NAC. Because SARS-CoV-2 is an enteric pathogen, the efficacy of LGG independent of etiology in the treatment of acute gastroenteritis is confirmed by our data.

Association of Short-Chain Fatty Acids with Gut Microbiota and Lipid Metabolism in Mice with Diarrhea Induced by High-Fat Diet in a Fatigued State.

Preliminary research finds that a high-fat diet (HFD) in a fatigued state triggers diarrhea, but the exact mechanism has not been clarified. To address concerns about the pathogenesis of diarrhea, the study evaluates the composition and metabolomics of the gut microbiota. The study uses the multiple platform apparatus device to induce fatigue in mice, combined with intragastric administration of lard-caused diarrhea. Subsequently, the characteristics and interaction relationship of gut microbiota, short-chain fatty acids (SCFAs), inflammatory biomarkers, brain-gut peptides, and lipid metabolism are analyzed at the end of the experiment. HFD in a fatigued state results in a significant increase in interleukin-17, interleukin-6, cholecystokinin, somatostatin, and malondialdehyde content in mice (p < 0.05), along with a substantial decrease in high-density lipoprotein (p < 0.05). Additionally, an HFD in a fatigued state causes changes in the structure and composition of the gut microbiota, with Lactobacillus murinus as its characteristic bacteria, and reduces the production of SCFAs. An HFD in a fatigued state triggers diarrhea, possibly associated with gut content microbiota dysbiosis, SCFAs deprivation, increased inflammation, and dysregulated lipid metabolism.

Metagenomic and metabolomic analyses reveal the role of gut microbiome-associated metabolites in diarrhea calves.

Calf diarrhea is a multifactorial disease that affects the cattle industry and accounts for more than 50% of calf mortality. Although there is evidence of an association between altered gut microbiota and diarrhea, remarkably little is known about the microbial and metabolic mechanisms underlying the link between gut microbiota dysbiosis and the occurrence of calf diarrhea. Here, we performed fecal metagenomic and metabolomic studies on fecal samples from diarrheic and healthy calves of Xia-nan cattle breed. Results revealed that composition of the gut microbiome and metabolome was remarkably altered in diarrheic calves, and gut microbial alterations were associated with diarrhea and linked to the changes in metabolites. Metabolite profiles showed that diarrheic calves exhibited a marked decrease in some purines (adenosine, adenine, 2'-deoxyguanosine, allantoate, deoxyinosine, and deoxyguanosine) and arachidonic acid (prostaglandin F2α and prostaglandin E2) compared to healthy calves. Purine-producing microbial species, including Lactiplantibacillus plantarum, Campylobacter coli, Treponema porcinum, Klebsiella pneumoniae, and Phocaeicola coprophilus, were significantly reduced in diarrheic calves compared to healthy calves, whereas the arachidonic acid-producing species such as Neisseria gonorrhoeae, Staphylococcus aureus, and Clostridiales bacterium exhibited a marked increase. These microbial signatures were closely associated with the metabolic dysbiosis of purine and arachidonic acid in diarrhea calves. Our study showed that gut microbiota-driven metabolic disorders of purine or arachidonic acid were associated with calf diarrhea. The findings prove that altered gut microbiota plays a role in diarrhea pathogenesis and indicate that gut microbiota-targeted therapies could be useful for both prevention and treatment of diarrhea. IMPORTANCE Calf diarrhea is of great concern to the global dairy industry as it results in significant economic losses due to lower conception rates, reduced milk production, and early culling. Although there is evidence of an association between altered gut microbiota and diarrhea, remarkably little is known about the microbial and metabolic mechanisms underlying the link between gut microbiota dysbiosis and the occurrence of calf diarrhea. Here, we used fecal metagenomic and metabolomic analyses to demonstrate that gut microbiota-driven metabolic disorders of purine or arachidonic acid were associated with calf diarrhea. These altered gut microbiotas play vital roles in diarrhea pathogenesis and indicate that gut microbiota-targeted therapies could be useful for both prevention and treatment of diarrhea.

Exploring the Benefits of Probiotics in Gut Inflammation and Diarrhea-From an Antioxidant Perspective.

Inflammatory bowel disease (IBD), characterized by an abnormal immune response, includes two distinct types: Crohn's disease (CD) and ulcerative colitis (UC). Extensive research has revealed that the pathogeny of IBD encompasses genetic factors, environmental factors, immune dysfunction, dysbiosis, and lifestyle choices. Furthermore, patients with IBD exhibit both local and systemic oxidative damage caused by the excessive presence of reactive oxygen species. This oxidative damage exacerbates immune response imbalances, intestinal mucosal damage, and dysbiosis in IBD patients. Meanwhile, the weaning period represents a crucial phase for pigs, during which they experience pronounced intestinal immune and inflammatory responses, leading to severe diarrhea and increased mortality rates. Pigs are highly similar to humans in terms of physiology and anatomy, making them a potential choice for simulating human IBD. Although the exact mechanism behind IBD and post-weaning diarrhea remains unclear, the oxidative damage, in its progression and pathogenesis, is well acknowledged. Besides conventional anti-inflammatory drugs, certain probiotics, particularly Lactobacillus and Bifidobacteria strains, have been found to possess antioxidant properties. These include the scavenging of reactive oxygen species, chelating metal ions to inhibit the Fenton reaction, and the regulation of host antioxidant enzymes. Consequently, numerous studies in the last two decades have committed to exploring the role of probiotics in alleviating IBD. Here, we sequentially discuss the oxidative damage in IBD and post-weaning diarrhea pathogenesis, the negative consequences of oxidative stress on IBD, the effectiveness of probiotics in IBD treatment, the application of probiotics in weaned piglets, and the potential antioxidant mechanisms of probiotics.

Mucin O-glycan-microbiota axis orchestrates gut homeostasis in a diarrheal pig model

BackgroundPost-weaning diarrhea in piglets reduces growth performance and increases mortality, thereby causing serious economic losses. The intestinal epithelial cells and microbiota reciprocally regulate each other in order to maintain intestinal homeostasis and control inflammation. However, a relative paucity of research has been focused on the host-derived regulatory network that controls mucin O-glycans and thereby changes gut microbiota during diarrhea in infancy. At the development stage just after birth, the ontogeny of intestinal epithelium, immune system, and gut microbiota appear similar in piglets and human infants. Here, we investigated the changes of mucin O-glycans associated with gut microbiota using a diarrheal post-weaned piglet model.ResultsWe found that diarrhea disrupted the colonic mucus layer and caused aberrant mucin O-glycans, including reduced acidic glycans and truncated glycans, leading to an impaired gut microenvironment. Subsequently, the onset of diarrhea, changes in microbiota and bacterial translocation, resulting in compromised epithelial barrier integrity, enhanced susceptibility to inflammation, and mild growth faltering. Furthermore, we found the activation of NLRP3 inflammasome complexes in the diarrheal piglets when compared to the healthy counterparts, triggered the release of proinflammatory cytokines IL-1β and IL-18, and diminished autophagosome formation, specifically the defective conversion of LC3A/B I into LC3A/B II and the accumulation of p62. Additionally, selective blocking of the autophagy pathway by 3-MA led to the reduction in goblet cell-specific gene transcript levels in vitro.ConclusionsWe observed that diarrheal piglets exhibited colonic microbiota dysbiosis and mucosal barrier dysfunction. Our data demonstrated that diarrhea resulted in the activation of inflammasomes and autophagy restriction along with aberrant mucin O-glycans including reduced acidic glycans and truncated glycans. The results suggested the mucin O-glycans-microbiota axis is likely associated with diarrheal pathogenesis. Our study provides novel insights into the pathophysiology of early-weaning-induced diarrheal disease in piglets and potentially understanding of disease mechanisms of diarrhea for human infants. Understanding the molecular pathology and pathogenesis of diarrhea is a prerequisite for the development of novel and effective therapies. Our data suggest that facilitating O-glycan elongation, modifying the microbiota, and developing specific inhibitors to some key inflammasomes could be the options for therapy of diarrhea including human infants.Graphical abstract79ZKnZ6nbqMhwNgSiMAsGZVideo abstract

A review of Leaves and Seeds Moringa oleifera Extract: The potential Moringa oleifera as Antibacterial, Anti-Inflammatory, Antidiarrhoeal, And Antiulcer Approaches To Bacterial Gastroenteritis

BACKGROUND: Bacterial gastroenteritis is a disease in the tropics in the form of inflammation of the stomach and intestines due to several bacteria, such as Salmonella, Campylobacter, Shigella, Escherichia coli, Vibrio, Yersinia, and Listeria with symptoms of diarrhea without or with vomiting and frequent fever. Gastroenteritis is a global disease with the highest prevalence in the agricultural community, especially farmers and fishermen. AIM: This research is to determine the potential of leaf and seed extract Moringa oleifera as an alternative therapy for bacterial gastroenteritis. METHODS: A literature review approach derived from the analysis and synthesis of various related references is used. The author selects journals full text and books published in the last ten years maximum through several databases, namely PubMed, Google Scholar, ScienceDirect, and Cochrane with the keywords: diarrhea, gastroenteritis, antibacterial, antiulcer, anti-inflammation, and M. oleifera. RESULTS: Seed and leaf extract M. oleifera played a role in preventing some of the effects of the pathogenesis of diarrhea due to bacterial infection. Methanol, N-hexane, ethyl acetate, flavonoids, phenols, saponins, alkaloids, tannins, and steroids from seed and leaf extract M. oleifera have antibacterial effects. The content of quercetin has an anti-inflammatory effect. The content of tannins, flavonoids, and alkaloids has antidiarrheal activity. The content of ethanol and tannins has an antiulcer effect. This potential can help cure patients with bacterial gastroenteritis. CONCLUSION: Leaf and seed extract of M. oleifera has good antibacterial, anti-inflammatory, antiulcer, and antidiarrheal potential for the treatment of bacterial gastroenteritis.

Gastrointestinal Candidiasis in Malnourished Children with Diarrhoea

It is known that the frequency of intestinal Candidiasis in infants and children below 3 years of age is very high, particularly in malnourished children. It has been shown also that Candida can reduce the absorption of sugar, water and electrolytes (Burke et al., I977; Thelen et al., I978).&#x0D; Recently we have studied the frequency of gastrointestinal Candidiasis and the Candida-killing-ability of leucocytes in Indonesian children.&#x0D; Species of Candida were found significantly more often in throat swabs, gastric, small intestinal contents and stools of malnourished children in comparison with specimens of reasonably well-nourished children.&#x0D; Furthermore there were marked qualitative differences in the species found in these groups according to their nutritional status.&#x0D; Studying the Candidacidal activity of leucocytes it shows that in malnourished children the killing-ability is significantly lower than in well-nourished children. These findings suggest that gastrointestinal Candidiasis may contribute to the pathogenesis of diarrhoea in malnourished children.

COVID-19-associated diarrhea

In addition to the typical clinical picture of respiratory symptoms and intoxication, the SARS-CoV-2 virus is also characterized by a gastroenterotropic effect. Diarrhea is one of the most common gastroenterological symptoms of COVID-19 and is detected, according to the various authors, in 2-49.5% of cases, including children. The presence of diarrhea aggravates the patient's clinical condition, limits the possibility of carrying out the necessary diagnostic manipulations, and complicates the selection of therapy. The article provides an overview of the scientific literature on the formation of diarrheal syndrome in patients with COVID-19. Objective. Analysis of scientific publications studying the pathogenesis, incidence, clinical features, aspects of diagnosis and therapy of diarrhea in patients with COVID-19. Material and methods. A search was made for scientific publications on the electronic resources PubMed, Google Scholar and eLIBRARY.ru. Results. The pathogenesis of diarrhea in a new coronavirus infection is complex and includes, among other things, the effect of the virus on the angiotensin-converting enzyme 2 receptors, inducing an inflammatory process in the gastrointestinal tract mucosa, neurotropic effect on the autonomic regulation of intestinal motor activity, disturbance of the colon microbiota, liver and pancreas damage. Another important pathogenetic aspect of diarrhea in COVID-19 is iatrogenic one, i.e. a side effect of drugs used in the treatment of a new coronavirus infection and its complications, and the activation of opportunistic clostridial intestinal flora against the background of antibiotic therapy. The variety of pathogenetic mechanisms of diarrheal syndrome formation allows us to speak of "COVID-associated diarrhea" as an independent clinical phenomenon characteristic for the new coronavirus infection. Mandatory diagnostic algorithm of a patient with COVID-19 and diarrhea is the fecal analysis test for toxins Cl. difficile, while the possibility of endoscopic examinations during the pandemic is limited. Compliance with the hygiene measures, diet correction and nutritional support, rational antibiotic therapy of COVID-19 complications, careful use of antiperistaltic antidiarrheal drugs, nonspecific therapy (antiviral, rehydration, adsorbents) are considered as the main therapeutic approaches for diarrheal syndrome against the background of COVID-19. The administration of probiotics and antibacterials should be considered in case of confirmed clostridial co-infection. Conclusion. Diarrhea is a frequent clinical manifestation of COVID-19 and can affect the course of the disease. The complex genesis of diarrheal syndrome requires further study of therapeutic strategies and nutritional support for patients after COVID-19.

Pathophysiology of neratinib-induced diarrhea in male and female rats: microbial alterations a potential determinant.

Neratinib is a potent irreversible pan-ErbB tyrosine kinase inhibitor, approved by the FDA for extended adjuvant treatment of HER2-positive breast cancer. Diarrhea is the most frequently observed adverse event with tyrosine kinase inhibitor therapy. In this study, we developed a reproducible model for neratinib-induced diarrhea in male and female rats. At first, male rats were treated with neratinib at 15, 30 or 50mg/kg or vehicle control via oral gavage for 28days (total n = 12). Secondly, we compared outcomes of male (n = 7) and female (n = 8) rats, treated with 50mg/kg neratinib. Rats treated with a 50mg/kg daily dose of neratinib had a reproducible and clinically relevant level of diarrhea and therefore was confirmed as an appropriate dose. Male rats treated with neratinib had significant changes to their gut microbiome. This included neratinib-induced increases in Ruminococcaceae (P = 0.0023) and Oscillospira (P = 0.026), and decreases in Blautia (P = 0.0002). On average, female rats experienced more significant neratinib-induced diarrhea (mean grade 1.526) compared with male rats (mean grade 1.182) (P < 0.0001). Neratinib caused a reduction in percentage weight gain after 28days of treatment in females (P = 0.0018) compared with vehicle controls. Females and males both showed instances of villus atrophy and fusion, most severely in the distal ileum. Serum neratinib concentration was higher in female rats compared to male rats (P = 0.043). A reproducible diarrhea model was developed in both female and male rats, which indicated that diarrhea pathogenesis is multifactorial, including anatomical disruption particularly evident in the distal ileum, and alterations in microbial composition.

P1737MICROBIOLOGICAL DIAGNOSIS OF DIARRHEA IN RENAL TRANSPLANT PATIENT BY MULTIPLEX PCR

Abstract Background and Aims Acute gastroenteritis is an unwelcome and harmful yet unavoidable complication in the renal transplant patient. Infections, especially atypical organisms like Norovirus, Cryptosporidium, along with typical microorganisms like E. coli and Giardia, form the significant players in the pathogenesis of diarrhea. Standard methods of staining and culture have reduced sensitivity as well as require considerable time for the reports. Stool Polymerase Chain Reaction (PCR)is a quick, sensitive, and hassle-free method that diagnoses more than 20 organisms within 1 hour. This study aims to determine the infective etiology of acute gastroenteritis in the transplant population as well to compare the yield of stool PCR with conservative methods. Method We retrospectively analyzed all renal transplant patients admitted between 2015 to 2018 with complaints of diarrhea (&amp;gt;3 stools/day with loose consistency). The sample was tested for conventional microbiological methods, including a stool routine for microscopy and culture. A stool sample was also sent for Multiplex PCR, which was analyzed by Bio Fire FilmArray GI Panel, which identifies 22 enteropathogens. Endoscopic procedures were also undertaken in suspected cases for CMV colitis and pseudomembranous colitis. Results 110 diarrheal events (admission for diarrhea) were recorded in 82 patients, with 181 organisms isolated in all samples. 16 events did not reveal any organisms in stool PCR. 85% sample yielded a positive result. The conventional method yielded a positive result in only 32.3% as compared to stool PCR. Co-infections were common, as 71.2% of events were associated with 2 or more organisms. Conventional methods failed to diagnose any co-infections. Norovirus G1/G2(20%) was the most common organism isolated from the stool, followed by Giardia (17%) and Enteropathogenic E. coli (16%). Giardia Lamblia with Norovirus G1/G2 was the most common co-infection in 19% of patients. Conclusion Stool PCR significantly improves the diagnostic yield in diagnosing enteric pathogens. Stool PCR is especially sensitive in detecting multiple organisms where conventional microbiological methods were completely unsuccessful. Norovirus is the most common enteropathogen, which is not picked by the conventional method. Giardia with Norovirus was the most common co-infection among post-transplant patients.

Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo-controlled clinical trial.

BackgroundMetronidazole is commonly administered to dogs with acute diarrhea, but there is limited evidence to support this practice.ObjectiveTo investigate the effects of metronidazole administration on dogs with acute nonspecific diarrhea.AnimalsThirty‐one dogs, including 14 test population dogs and 17 controls.MethodsRandomized controlled clinical trial. Dogs with acute diarrhea in which causation was not determined by routine fecal diagnostic testing were randomly assigned to metronidazole treatment (10‐15 mg/kg PO q12h for 7 days) or placebo. Fecal cultures and characterization of Clostridium perfringens isolates also were performed. Owners maintained medication and fecal scoring logs, and fecal diagnostic tests were repeated on day 7.ResultsThe mean ± SD time to resolution of diarrhea for test population dogs (2.1 ± 1.6 days) was less than that for controls (3.6 ± 2.1 days, P = .04). Potential relationships of C. perfringens with acute diarrhea pathogenesis were not investigated, but only 3 of 13 (23.1%) test population dogs had persistent C. perfringens carriage at day 7, which was less than the 11 of 14 (78.6%) controls with persistent growth (P = .007).Conclusions and Clinical ImportanceOur results suggest that metronidazole treatment can shorten duration of diarrhea and decrease fecal culture detection of C. perfringens in some dogs with acute nonspecific diarrhea. Additional studies are needed to assess the benefits and risks of routine use of metronidazole for this purpose because most dogs achieve resolution of diarrhea within several days regardless of treatment.

Commercial vs. Natural Food-based Tube Feeding on Diarrhea Incidence in Critically Ill Cardiac Surgery Patients (P12-030-19)

ObjectivesDiarrhea has negative consequences on health outcomes of critically ill patients administered with enteral feeding. Diarrhea pathogenesis in these patients is associated with several factors, including the administration of commercial enteral formulas providing nutrients and food without the natural food matrix. However, the potential benefits of natural food-based tube feeding on gastrointestinal complications have not been well established yet. The present study aimed at examining the effect of natural-based tube feeding on diarrhea incidence in critically ill cardiac surgery patients. MethodsRetrospective medical chart review of adult patients admitted postoperatively to a Cardiac Surgery Intensive Care Unit and administered with tube feeding. Two cohorts of patients were identified, one administered with blenderized natural food (BNF) and the other one with standard commercial formula (SCF). In the study setting, there was a switch from SCF to BNF starting from 01/01/2015. The two cohorts were identified according to such a time criterion. Time to the first event of diarrhea, defined as the presence of loose or watery stool - at least 3-time per day - according to the Bristol Stool Chart type, was the primary study outcome. A crude comparison of the time to the first event of diarrhea between SCF and BNF cohorts was carried out using Kaplan-Meier curves. Differences in survival rates between groups were assessed with the Log-Rank test. The adjusted comparison was performed by fitting a multivariable Cox Proportional-Hazards (PH) model. ResultsTwo-hundred and ten patients were considered in the study (99 in the BNF cohort). No significant differences were identified in patients’ baseline characteristics. At crude analysis, the likelihood of diarrhea occurrence was significantly lower for subjects in the BNF compared to those in the SCF cohort (p-value 0.017). At adjusted analysis, BNF almost halved the risk of experiencing diarrhea (Hazard Ration of diarrhea in BNF patients compared to SCF ones of 0.554, 95% CI: 0.327–0.938, p-value 0.02). ConclusionsIn a population of postoperative cardiac surgery patients, a BNF diet was found to reduce the risk of diarrhea significantly. The present study provides new insights into the nutritional management of critically ill patients. Funding SourcesUnit of Biostatistics, Epidemiology and Public Health, University of Padova, Padova, Italy.

The Correlation Between Vitamin D and Bacterial Diarrhea in Children

Background: Acute diarrhea is the most common gastrointestinal disease among children. Identification of factors involved in the pathogenesis of acute bacterial diarrhea is highly critical. Objectives: This study was conducted to investigate the correlation between serum 25-hydroxyvitamin D (25 (OH) Vit. D) and acute bacterial diarrhea in children. Methods: The present study compared 60 children with acute bacterial diarrhea (the case group) and 60 healthy children (the control group) for serum 25 (OH) Vit. D concentrations. The children age ranged from two months to 12 years. The serum 25-hydroxyvitamin D level was measured using ELISA method. Results: Among 60 children with acute bacterial diarrhea, 38 (63.3%) were males and 22 (36.7%) females. In the control group, 31 (51.6%) were males and 29 (48.4%) females (P = 0.26). The median (IQR) of age in case and control groups were 16 (29) and 16 (24) months, respectively (P = 0.75). The mean ± SD of serum 25 (OH) Vit. D levels in case and control groups were 19.3 ± 7.8 and 22.4 ± 7.3 ng/mL, respectively. There was a significant difference between groups regarding the serum 25 (OH) Vit. D concentrations (P = 0.02). Conclusions: This study revealed a significant correlation between serum 25 (OH) Vit. D level and acute bacterial diarrhea. It is likely that vitamin D plays a role in the pathogenesis of diarrhea.

Illumina MiSeq Sequencing Investigation of Microbiota in Bronchoalveolar Lavage Fluid and Cecum of the Swine Infected with PRRSV.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant animal morbidity and mortality and economic losses worldwide. In this study, we analyzed the microbiota in bronchoalveolar lavage fluid (BAL), mucosa, and feces in cecum of the PRRSV-challenged pigs using the Illumina MiSeq sequencing platform, to investigate the role of microbiota in the pathogenesis and development of porcine reproductive and respiratory syndrome (PRRS). Quantitative insights into microbial ecology analyses indicated that the dominant bacterial groups in the lung from the PRRSV-challenged pigs were Haemophilus parasuis and Mycoplasma hyorhinis, with a relative abundance of 35-48% and 27-41%, respectively. Our results were consistent with the clinical observation that the PRRSV-infected pigs are always co-infected with other bacteria, such as Haemophilus and Mycoplasma. On the other hand, Campylobacter and Clostridium became the two most abundant bacteria in the mucosal and luminal microbiota of the cecum of the PRRSV-challenged pigs, and the relative abundance was four times higher than that in the healthy pigs. This suggested that Campylobacter and Clostridium might be associated with the pathogenesis of diarrhea in PRRS. Linear discriminant analysis effect size reveals significant microbial dysbiosis of BAL, mucosa, and feces in cecum of the PRRSV-challenged pigs. We have identified a structural imbalance of the microbiota, characterized by a reduced diversity of microbiota and abundance alterations of certain bacteria in the PRRSV-challenged pigs. The observed microbiota dysbiosis in this study provides insight into the roles of the microbiota in the complications of the PRRSV infection.

Changes in circRNA expression profiles related to the antagonistic effects of Escherichia coli F17 in lamb spleens

Sheep colibacillosis is one of the most common bacterial diseases in large-scale sheep farms. In this study, we orally administered Escherichia coli F17 (E. coli F17) to lambs to obtain antagonistic and sensitive individuals. We used RNA-seq to screen for differential circRNAs in the spleens of both antagonist and sensitive individuals to explore the effect of circRNA on anti-diarrhoea in sheep. The results showed that 60 differentially expressed (DE) circRNAs were screened by RNA-seq in the spleen of antagonistic and sensitive lambs, among which 31 were up-regulated and 29 were down-regulated; q-PCR was used to validate the relative expression levels of six randomly selected circRNAs in antagonist and susceptible lambs and found to be consistent with the results of RNA-seq. Using Miranda analysis of circRNA-miRNA-mRNA interactions, we found a certain target relationship between 6 circRNAs, 5 miRNAs and 9 mRNAs. The relative expression levels of mRNA in antagonistic and sensitive lambs were verified by q-PCR and were consistent with the results of RNA-seq. This study explored the expression profile of circRNA in the spleen of an antagonistic and susceptible lamb with diarrhoea and found that differentially expressed circRNAs were helpful for determining how the lambs resist the pathogenesis of diarrhoea and provided a scientific basis for lambs to resist diarrhoea.

Tumor Necrosis Factor alpha (TNFα) reduces intestinal ascorbic acid (AA) uptake

Intestinal inflammation and systemic bacterial infection are associated with an increase in the level of proinflammatory cytokines like tumor necrosis factor alpha (TNFα) in the intestinal mucosa and blood. Though important for intestinal immunity, TNFα also exerts profound effects on intestinal absorptive and secretory functions through specific intracellular signaling pathways like NF‐κB. Studies have shown that high levels of TNFα are linked to the pathogenesis of diarrhea in inflammatory bowel disease (IBD) and that these patients have low levels of vitamin C. To date, however, there has been little known about the effect of TNFα on intestinal absorption of vitamin C. Ouraim in this study was to address this issue using in vitro (Caco‐2), in vivo(mice), and ex vivo (enteroids) models, together with an array of physiological and molecular biological techniques. TreatingCaco‐2 cells and mice with TNFα led to a significant inhibition of 14C‐AAuptake compared to untreated controls. This inhibition was associated with significant decreases in SVCT‐1 protein, mRNA and hnRNA levels in TNFα treated Caco‐2 cells, mouse jejunum, and enteroids compared to their appropriate controls. TNFα also caused a significant inhibition in the activity of the SLC23A1 promoter in Caco‐2 cells. Further, treating Caco‐2 cells with the NF‐κB inhibitor celastrol blocked the inhibitory effect caused by TNFα on AA uptake, SVCT‐1 protein and mRNA expression, as well as SLC23A1 promoter activity. Finally, treatment of Caco‐2 cells with TNFα lead to a significant inhibition in the expression of the hepatocyte nuclear factor‐1α (HNF1α), which is known to drive the transcription of SLC23A1 promoter. Together, these findings demonstrate that TNFα inhibits intestinal AA uptake and that this effect is exerted, at least in part, at the level of transcription of the SLC23A1 gene through NF‐κB signaling pathway.Support or Funding InformationSupported by NIH grants DK 107474, DK 58057, DK 56057 and a grant from the DVA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of bile acids in inflammatory bowel disease.

Bile acids (BAs) are the end product of cholesterol catabolism. Their synthesis is regulated by the nuclear receptor farnesoid X receptor, also involved in the control of their enterohepatic circulation. Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial diseases characterized by diarrhea. The pathogenesis of diarrhea in IBD is still debated. The most important factor is the inflammatory process of the intestinal wall, causing alterations of solute and water absorption/secretion, deterioration of epithelial cell integrity, disruption of the intestinal microflora homeostasis, and impairment of specific transport mechanisms within the gut (including that of BAs). In this review, we summarize the current state of the art in this area and we critically evaluate the alterations of BA metabolism in patients with CD and UC.