[A case of eosinophilic gastroenteritis caused after the use of Seprafilm®].

Eosinophilic gastroenteritis is a fairly uncommon condition. It has been suggested that allergic reactions may have played a role in the development of this illness. The case of a 66-year-old woman who had a total hysterectomy due to a right ovarian tumor is described here. At this operation, a sodium hyaluronate carboxymethylcellulose bioresorbable membrane (Seprafilm®) was used. She was admitted to our hospital 47 days after the operation with abdominal pain. Laboratory data indicated elevated WBC (29450/µl) and eosinophilia (69.2%), and CT scan showed thickening of intestinal wall and ascites around there. Ascites cytology showed a significant increase of eosinophils (94.0%). She began taking oral steroids after being diagnosed with eosinophilic gastroenteritis, and her symptoms improved quickly. Despite the fact that Seprafilm® was thought to be a reliable and safe tool, it was suggested that a foreign body reaction to Seprafilm® could lead to eosinophilic gastroenteritis.

Ebola virus delta peptide is an enterotoxin.

During the 2013-2016 West African (WA) Ebola virus (EBOV) outbreak, severe gastrointestinal symptoms were common in patients and associated with poor outcome. Delta peptide is a conserved product of post-translational processing of the abundant EBOV soluble glycoprotein (sGP). The murine ligated ileal loop model was used to demonstrate that delta peptide is a potent enterotoxin. Dramatic intestinal fluid accumulation follows injection of biologically relevant amounts of delta peptide into ileal loops, along with gross alteration of villous architecture and loss of goblet cells. Transcriptomic analyses show that delta peptide triggers damage response and cell survival pathways and downregulates expression of transporters and exchangers. Induction of diarrhea by delta peptide occurs via cellular damage and regulation of genes that encode proteins involved in fluid secretion. While distinct differences exist between the ileal loop murine model and EBOV infection in humans, these results suggest that delta peptide may contribute to EBOV-induced gastrointestinal pathology.

High-Fat Diet-Induced Obesity Aggravates Food Allergy by Intestinal Barrier Destruction and Inflammation.

INTRODUCTION: The increase in high-fat diet (HFD)-induced obesity and food allergy leads to an assumption that the 2 are related. This study aims to (1) systematic verification of HFD-induced obesity aggravates food allergy and (2) explore the correlation and molecular mechanisms of HFD-induced obesity promotes food allergy. METHODS: Female BALB/c mice are divided into the control group (control), the ovalbumin (OVA)-sensitized group (OVA), the HFD-induced obesity group (HFD), and HFD-induced allergic obesity group (HFD + OVA). RESULTS: In vivo data showed that HFD feed enhance clinical symptoms and intestinal mucosa villi shed on allergic mice. Moreover, we found that HFD and OVA irritation enhanced levels of mast cell degranulation and Th2 humoral response. Additionally, Western blot analysis showed the potentiation of peroxisome proliferator-activated receptor γ (PPAR γ) remarkably reduced on intestinal in HFD and OVA group, thereby inhibiting the expression of nuclear factor kappa B (NF-κB)/PPAR γ signal the phosphorylation of NF-κB P65. CONCLUSIONS: Overall, our results suggest that HFD-induced obesity is a potential risk factor for food allergy, which related to intestinal barrier destruction and inflammation through the PPAR γ/NF-κB signaling pathway.

Reduction in Severity of All-Cause Gastroenteritis Requiring Hospitalisation in Children Vaccinated against Rotavirus in Malawi.

Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix® rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis presented in children requiring hospitalisation remains unknown. We conducted a hospital-based surveillance study to assess the impact of Rotarix® vaccination on the severity of gastroenteritis presented by Malawian children. Stool samples were collected from children aged <5 years who required hospitalisation with acute gastroenteritis from December 2011 to October 2019. Gastroenteritis severity was determined using Ruuska and Vesikari scores. Rotavirus was detected using enzyme immunoassay. Rotavirus genotypes were determined using nested RT-PCR. Associations between Rotarix® vaccination and gastroenteritis severity were investigated using adjusted linear regression. In total, 3159 children were enrolled. After adjusting for mid-upper arm circumference (MUAC), age, gender and receipt of other vaccines, all-cause gastroenteritis severity scores were 2.21 units lower (p < 0.001) among Rotarix®-vaccinated (n = 2224) compared to Rotarix®-unvaccinated children (n = 935). The reduction in severity score was observed against every rotavirus genotype, although the magnitude was smaller among those infected with G12P[6] compared to the remaining genotypes (p = 0.011). Each one-year increment in age was associated with a decrease of 0.43 severity score (p < 0.001). Our findings provide additional evidence on the impact of Rotarix® in Malawi, lending further support to Malawi's Rotarix® programme.

From a case-control survey to a diagnostic viral gastroenteritis panel for testing of general practitioners' patients.

OBJECTIVE: To evaluate the pathogenicity of a broad range of 11 possible gastroenteritis viruses, by means of statistical relationships with cases vs. controls, or Ct-values, in order to establish the most appropriate diagnostic panel for our general practitioner (GP) patients in the Netherlands (2010-2012). METHODS: Archived stool samples from 1340 cases and 1100 controls were retested using internally controlled multiplex real-time PCRs for putative pathogenic gastroenteritis viruses: adenovirus, astrovirus, bocavirus, enterovirus, norovirus GI and GII, human parechovirus, rotavirus, salivirus, sapovirus, and torovirus. RESULTS: The prevalence of any virus in symptomatic cases and asymptomatic controls was 16.6% (223/1340) and 10.2% (112/1100), respectively. Prevalence of astrovirus (adjusted odds ratio (aOR) 10.37; 95% confidence interval (CI) 1.34-80.06) and norovirus GII (aOR 3.10; CI 1.62-5.92) was significantly higher in cases versus controls. Rotavirus was encountered only in cases. We did not find torovirus and there was no statistically significant relationship with cases for salivirus (aOR 1,67; (CI) 0.43-6.54)), adenovirus non-group F (aOR 1.20; CI 0.75-1.91), bocavirus (aOR 0.85; CI 0.05-13.64), enterovirus (aOR 0.83; CI 0.50-1.37), human parechovirus (aOR 1.61; CI 0.54-4.77) and sapovirus (aOR 1.15; CI 0.67-1.98). Though adenovirus group F (aOR 6.37; CI 0.80-50.92) and norovirus GI (aOR 2.22, CI: 0.79-6.23) are known enteropathogenic viruses and were more prevalent in cases than in controls, this did not reach significance in this study. The Ct value did not discriminate between carriage and disease in PCR-positive subjects. CONCLUSIONS: In our population, diagnostic gastroenteritis tests should screen for adenovirus group F, astrovirus, noroviruses GI and GII, and rotavirus. Case-control studies as ours are lacking and should also be carried out in populations from other epidemiological backgrounds.

cGAS-STING effectively restricts murine norovirus infection but antagonizes the antiviral action of N-terminus of RIG-I in mouse macrophages.

Although cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling has been well recognized in defending DNA viruses, the role of cGAS-STING signaling in regulating infection of RNA viruses remains largely elusive. Noroviruses, as single-stranded RNA viruses, are the main causative agents of acute viral gastroenteritis worldwide. This study comprehensively investigated the role of cGAS-STING in response to murine norovirus (MNV) infection. We found that STING agonists potently inhibited MNV replication in mouse macrophages partially requiring the JAK/STAT pathway that induced transcription of interferon (IFN)-stimulated genes (ISGs). Loss- and gain-function assays revealed that both cGAS and STING were necessary for host defense against MNV propagation. Knocking out cGAS or STING in mouse macrophages led to defects in induction of antiviral ISGs upon MNV infection. Overexpression of cGAS and STING moderately increased ISG transcription but potently inhibited MNV replication in human HEK293T cells ectopically expressing the viral receptor CD300lf. This inhibitory effect was not affected by JAK inhibitor treatment or expression of different MNV viral proteins. Interestingly, STING but not cGAS interacted with mouse RIG-I, and attenuated its N-terminus-mediated anti-MNV effects. Our results implicate an essential role for mouse cGAS and STING in regulating innate immune response and defending MNV infection. This further strengthens the evidence of cGAS-STING signaling in response to RNA virus infection.

PGD2 and CRTH2 counteract Type 2 cytokine-elicited intestinal epithelial responses during helminth infection.

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD2 and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine-mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD2-CRTH2 pathway negatively regulates the Type 2 cytokine-driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.

Bacteroides uniformis CECT 7771 alleviates inflammation within the gut-adipose tissue axis involving TLR5 signaling in obese mice.

This study investigated the immune mechanisms whereby administration of Bacteroides uniformis CECT 7771 reduces metabolic dysfunction in obesity. C57BL/6 adult male mice were fed a standard diet or a Western diet high in fat and fructose, supplemented or not with B. uniformis CECT 7771 for 14 weeks. B. uniformis CECT 7771 reduced body weight gain, plasma cholesterol, triglyceride, glucose, and leptin levels; and improved oral glucose tolerance in obese mice. Moreover, B. uniformis CECT 7771 modulated the gut microbiota and immune alterations associated with obesity, increasing Tregs and reducing B cells, total macrophages and the M1/M2 ratio in both the gut and epididymal adipose tissue (EAT) of obese mice. B. uniformis CECT 7771 also increased the concentration of the anti-inflammatory cytokine IL-10 in the gut, EAT and peripheral blood, and protective cytokines TSLP and IL-33, involved in Treg induction and type 2 innate lymphoid cells activation, in the EAT. It also restored the obesity-reduced TLR5 expression in the ileum and EAT. The findings indicate that the administration of a human intestinal bacterium with immunoregulatory properties on the intestinal mucosa helps reverse the immuno-metabolic dysfunction caused by a Western diet acting over the gut-adipose tissue axis.

Etiological, epidemiological, and clinical features of acute diarrhea in China.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged <5 years had higher overall positive rate of viral pathogens, while bacterial pathogens were more common in patients aged 18‒45 years. A joinpoint analysis revealed the age-specific positivity rate and how this varied for individual pathogens. Our findings fill crucial gaps of how the distributions of enteropathogens change across China in patients with diarrhea. This allows enhanced identification of the predominant diarrheal pathogen candidates for diagnosis in clinical practice and more targeted application of prevention and control measures.

Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body.

Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host-microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host's metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota-host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.

Paneth cells mediated the response of intestinal stem cells at the early stage of intestinal inflammation in the chicken.

The rapid renewal and repair of the intestinal mucosa are based on intestinal stem cells (ISC), which are located at the crypt bottom. Paneth cells are an essential component in the crypt, which served as the niche for ISC development. However, in the chicken, how the function of Paneth cells changes during intestinal inflammation is unclear and is the key to understand the mechanism of mucosal repair. In the present study, 36 HyLine White chickens (7 d of age, n = 6) were randomly divided into 1 control and 5 lipopolysaccharide (LPS) injection groups. The chickens were injected (i.p.) with PBS in the control group, however, were injected (i.p.) with LPS (10 mg/kg BW) in the LPS injection groups, which would be sampled at 5 time points (1 h postinjection [hpi], 2 hpi, 4 hpi, 6 hpi, and 8 hpi). Results showed that tumor necrosis factor-α mRNA transcription in duodenal tissue increased gradually since 1 hpi, peaked at 4 hpi, and then reduced remarkably, indicating that 4 hpi of LPS was the early stage of intestinal inflammation. Meanwhile, the MUC2 expression in duodenal tissue was dramatically reduced since 1 hpi of LPS. The ISC marker, Lgr5 and Bmi1, in the duodenal crypt were reduced from 1 hpi to 4 hpi and elevated later. Accordingly, the hydroethidine staining showed that the reactive oxygen species level, which drives the differentiation of ISC, in the duodenal crypt reduced obviously at 1 hpi and recovered gradually since 4 hpi. The analysis of Paneth cells showed that many swollen mitochondria appeared in Paneth cells at 4 hpi of LPS. Meanwhile, the Lysozyme transcription in the duodenal crypt was substantially decreased since 1 hpi of LPS. However, the Wnt3a and Dll1 in duodenal crypt decreased at 1 hpi of LPS, then increased gradually. In conclusion, Paneth cells were impaired at the early stage of intestinal inflammation, then recovered rapidly. Thus, the ISC activity was reduced at first and recovery soon.

Gastrointestinal ultrasonographic findings in cats with Feline panleukopenia: a case series.

BACKGROUND: Feline panleukopenia virus (FPV) is very resistant and highly contagious and infects domestic cats and other felids. FPV is particularly widespread among sheltered cats, and is associated with high morbidity and mortality, causing severe gastroenteritis characterized by anorexia, lethargy, fever, dehydration, hemorrhagic diarrhea, and vomiting. There is currently no data on the ultrasonographic features of cats affected with FPV. This case series describes abdominal ultrasonographic findings in shelter cats with naturally-occurring FPV, and assesses whether are associated with clinical and laboratory findings. Cats affected by FPV were enrolled in the study if an abdominal ultrasound was performed within 12 hours of diagnosis. Clinical, laboratory and survival data were collected from medical records. Ultrasonographic examinations were reviewed for gastrointestinal abnormalities and their associations with the above data were explored. RESULTS: Twenty-one cats were included. Nine cats (42.9%) died and 12 (57.1%) recovered. Based on ultrasonography, the duodenum and jejunum showed thinning of the mucosal layer in 70.6% and 66.6% of cats, thickening of the muscular layer in 52.9% and 57.1% of cats, and hyperechogenicity of the mucosa in 41.2% and 33.3%. Jejunal hyperechoic mucosal band paralleling the submucosa and irregular luminal surface were both observed in 33.3% of the cats. Survival was positively associated with increased jejunal mucosal echogenicity (P = 0.003) and hyperechoic mucosal band (P = 0.003). Peritoneal free fluid was positively associated with vomiting (P = 0.002). CONCLUSIONS: This study provides ultrasonographic features of naturally-occurring FPV in cats, which, as expected, are compatible with gastroenteropathy. The most frequent findings were diffuse small intestine mucosal layer thinning, muscular layer thickening and mucosal hyperechogenicity, jejunal hyperechoic mucosal band and irregular luminal surface. Ultrasonographic features may be useful to complete the clinical picture and assess the severity of the gastroenteropathy in FPV cats. Prospective studies are needed to confirm ultrasonographic prognostic factors.

Human Noroviruses Attach to Intestinal Tissues of a Broad Range of Animal Species.

Human noroviruses are the most common nonbacterial cause of gastroenteritis outbreaks, with new variants and genotypes frequently emerging. The origin of these new viruses is unknown; however, animals have been proposed as a potential source, as human noroviruses have been detected in animal species. Here, we investigated the potential of animals to serve as a reservoir of human noroviruses by testing norovirus attachment to formalin-fixed intestinal tissues of a range of potential reservoir animals. We set up a novel method to study norovirus binding using fluorescein isothiocyanate (FITC)-labeled virus-like particles (VLPs). In humans, noroviruses interact with histo-blood group antigens (HBGAs), carbohydrates that are expressed, among others, on the epithelial lining of the gastrointestinal tract. In animals, this interaction is not well understood. To test if virus binding depends on HBGAs, we characterized the HBGA phenotype in animal tissues by immunohistochemistry. With the exception of the black-headed gull and the straw-colored fruitbat, we observed the attachment of several human norovirus genotypes to the intestinal epithelium of all tested animal species. However, we did not find an association between the expression of a specific HBGA phenotype and virus-like particle (VLP) attachment. We show that selected human noroviruses can attach to small-intestinal tissues across species, supporting the hypothesis that human noroviruses can reside in an animal reservoir. However, whether this attachment can subsequently lead to infection needs to be further assessed.IMPORTANCE Noroviruses are a major cause of acute gastroenteritis in humans. New norovirus variants and recombinants (re)emerge regularly in the human population. From animal experiments and surveillance studies, it has become clear that at least seven animal models are susceptible to infection with human strains and that domesticated and wild animals shed human noroviruses in their feces. As virus attachment is an important first step for infection, we used a novel method utilizing FITC-labeled VLPs to test for norovirus attachment to intestinal tissues of potential animal hosts. We further characterized these tissues with regard to their HBGA expression, a well-studied norovirus susceptibility factor in humans. We found attachment of several human strains to a variety of animal species independent of their HBGA phenotype. This supports the hypothesis that human strains could reside in an animal reservoir.

The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model.

BACKGROUND & AIMS: Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. METHODS: Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. RESULTS: Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid-Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. CONCLUSIONS: Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.

Microbiota attenuates chicken transmission-exacerbated campylobacteriosis in Il10-/- mice.

Campylobacter jejuni is a prevalent foodborne pathogen mainly transmitting through poultry. It remains unknown how chicken-transmitted C. jejuni and microbiota impact on human campylobacteriosis. Campylobacter jejuni AR101 (Cj-P0) was introduced to chickens and isolated as passage 1 (Cj-P1). Campylobacter jejuni Cj-P1-DCA-Anaero was isolated from Cj-P0-infected birds transplanted with DCA-modulated anaerobic microbiota. Specific pathogen free Il10-/- mice were gavaged with antibiotic clindamycin and then infected with Cj-P0, Cj-P1, or Cj-P1-DCA-Anaero, respectively. After 8 days post infection, Il10-/- mice infected with Cj-P1 demonstrated severe morbidity and bloody diarrhea and the experiment had to be terminated. Cj-P1 induced more severe histopathology compared to Cj-P0, suggesting that chicken transmission increased C. jejuni virulence. Importantly, mice infected with Cj-P1-DCA-Anaero showed attenuation of intestinal inflammation compared to Cj-P1. At the cellular level, Cj-P1 induced more C. jejuni invasion and neutrophil infiltration into the Il10-/- mouse colon tissue compared to Cj-P0, which was attenuated with Cj-P1-DCA-Anaero. At the molecular level, Cj-P1 induced elevated inflammatory mediator mRNA accumulation of Il17a, Il1ß, and Cxcl1 in the colon compared to Cj-P0, while Cj-P1-DCA-Anaero showed reduction of the inflammatory gene expression. In conclusion, our data suggest that DCA-modulated anaerobes attenuate chicken-transmitted campylobacteriosis in mice and it is important to control the elevation of C. jejuni virulence during chicken transmission process.

The Impact of Circulating Antibody on Group B Streptococcus Intestinal Colonization and Invasive Disease.

Gastrointestinal (GI) colonization with group B Streptococcus (GBS) is an important precursor to late-onset (LO) disease in infants. The host-pathogen interactions that mediate progression to invasive disease remain unknown due, in part, to a paucity of robust model systems. Passively acquired maternal GBS-specific antibodies protect newborns from early-onset disease, yet their impact on GI colonization and LO disease is unexplored. Using murine models of both perinatal and postnatal GBS acquisition, we assessed the kinetics of GBS GI colonization, progression to invasive disease, and the role of GBS-specific IgG production in exposed offspring and juvenile mice at age 12 and 14 days, respectively. We defined LO disease as >7 days of life in the perinatal model. We studied the impact of maternal immunization using a whole-cell GBS vaccine on the duration of intestinal colonization and progression to invasive disease after postnatal GBS exposure in offspring. Animals exhibit sustained GI colonization following both perinatal and postnatal exposure to GBS, with 21% and 27%, respectively, developing invasive disease. Intestinal colonization with GBS induces an endogenous IgG response within 20 days of exposure. Maternal vaccination with whole-cell GBS induces production of GBS-specific IgG in dams that is vertically transmitted to their offspring but does not decrease the duration of GBS intestinal colonization or reduce LO mortality following postnatal GBS exposure. Both perinatal and postnatal murine models of GBS acquisition closely recapitulate the human disease state, in which GBS colonizes the intestine and causes LO disease. We demonstrate both endogenous production of anti-GBS IgG in juvenile mice and vertical transfer of antibodies to offspring following maternal vaccination. These models serve as a platform to study critical host-pathogen interactions that mediate LO GBS disease.

Necroptosis in Intestinal Inflammation and Cancer: New Concepts and Therapeutic Perspectives.

Necroptosis is a caspases-independent programmed cell death displaying intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development such tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis plays a role in many disease conditions and inhibiting necroptosis is currently considered a promising therapeutic strategy. In this review, we focus on the molecular mechanisms of necroptosis as well as its involvement in human diseases. We also discuss the present developing therapies that target necroptosis machinery.

Detection of an unusual G8P[8] rotavirus in a Rotarix-vaccinated child with acute gastroenteritis using Nanopore MinION sequencing: A case report.

RATIONALE: Rotavirus is routinely diagnosed by the detection of antigens or the viral genome. However, these tests have limitations, in that they do not detect all rotavirus strains. PATIENT CONCERNS: We present a case of a 27-month-old girl who was hospitalized for 4 days with severe gastroenteritis, including high fever, vomiting, diarrhea, mild dehydration, and periumbilical pain. Notably, the patient previously received the Rotarix vaccine. DIAGNOSES: The laboratory tests were negative for rotavirus, astrovirus, adenovirus, and norovirus as well as common diarrhea-causing bacteria. Human-bovine recombinant rotavirus was detected by MinION sequencing. INTERVENTIONS: To investigate the cause agents from the unexplained severe gastroenteritis infant, the stool sample was prepared by random amplification for Nanopore MinION sequencing. OUTCOMES: Treatment through the administration of ORS solution and galtase powder with probiotics was successful after the diagnosis of unusual rotavirus infection. LESSONS: This case report is the first detection of an unusual human-bovine recombinant rotavirus in an idiopathic gastroenteritis using Nanopore MinION sequencing.

Obesity Worsens Gulf War Illness Symptom Persistence Pathology by Linking Altered Gut Microbiome Species to Long-Term Gastrointestinal, Hepatic, and Neuronal Inflammation in a Mouse Model.

Persistence of Gulf War illness (GWI) pathology among deployed veterans is a clinical challenge even after almost three decades. Recent studies show a higher prevalence of obesity and metabolic disturbances among Gulf War veterans primarily due to the existence of post-traumatic stress disorder (PTSD), chronic fatigue, sedentary lifestyle, and consumption of a high-carbohydrate/high-fat diet. We test the hypothesis that obesity from a Western-style diet alters host gut microbial species and worsens gastrointestinal and neuroinflammatory symptom persistence. We used a 5 month Western diet feeding in mice that received prior Gulf War (GW) chemical exposure to mimic the home phase obese phenotype of the deployed GW veterans. The host microbial profile in the Western diet-fed GWI mice showed a significant decrease in butyrogenic and immune health-restoring bacteria. The altered microbiome was associated with increased levels of IL6 in the serum, Claudin-2, IL6, and IL1ß in the distal intestine with concurrent inflammatory lesions in the liver and hyperinsulinemia. Microbial dysbiosis was also associated with frontal cortex levels of increased IL6 and IL1ß, activated microglia, decreased levels of brain derived neurotrophic factor (BDNF), and higher accumulation of phosphorylated Tau, an indicator of neuroinflammation-led increased risk of cognitive deficiencies. Mechanistically, serum from Western diet-fed mice with GWI significantly increased microglial activation in transformed microglial cells, increased tyrosyl radicals, and secreted IL6. Collectively, the results suggest that an existing obese phenotype in GWI worsens persistent gastrointestinal and neuronal inflammation, which may contribute to poor outcomes in restoring cognitive function and resolving fatigue, leading to the deterioration of quality of life.