Intestinal Infections Research Articles

Caenorhabditis elegans immune responses to microsporidia and viruses

The model organism Caenorhabditis elegans is susceptible to infection by obligate intracellular pathogens, specifically microsporidia and viruses. These intracellular pathogens infect intestinal cells, or, for some microsporidia, epidermal cells. Strikingly, intestinal cell infections by viruses or microsporidia trigger a common transcriptional response, activated in part by the ZIP-1 transcription factor. Among the strongest activated genes in this response are ubiquitin-pathway members and members of the pals family, an intriguing gene family with cross-regulations of different members of genomic clusters. Some of the induced genes participate in host defense against the pathogens, for example through ubiquitin-mediated inhibition. Other mechanisms defend the host specifically against viral infections, including antiviral RNA interference and uridylation. These various immune responses are altered by environmental factors and by intraspecific genetic variation of the host. These pathogens were first isolated 15 years ago and much remains to be discovered using C. elegans genetics; also, other intracellular pathogens of C. elegans may yet to be discovered.

Helicobacter Pylori and Intestinal Parasites Co-infection in Pregnant Women Attending Antenatal Clinic in a Hospital, South-South Nigeria

Pregnant women are susceptible to severe health problems caused by Helicobacter pylori and intestinal parasitic infections. These conditions include iron deficiency anaemia, hyperemesis gravidarum, gastritis, duodenal ulcers, and maternal morbidity and mortality. These infections usually spread due to poor personal hygiene and socioeconomic conditions. The study aimed to investigate the occurrence of H. pylori and intestinal parasitic infections amongst pregnant women attending the antenatal clinic in Okolobiri, Bayelsa State. We analysed the samples using the H. pylori antibody rapid tests, stool direct wet mounts, formal ether concentration, and saturated sodium chloride floatation. The data revealed that 34% of the women were infected with H. pylori and 20% with intestinal parasites. The highest occurrence of H. pylori infection and intestinal co-infection was in the 26-30 age group. Entamoeba histolytica was the most common type of protozoa present, while Ascaris lumbricoides and Trichuris trichuria were the most common forms of helminth infections. The Chi-square analysis showed a statistically significant difference with respect to age. These results provide essential epidemiological data on the prevalence of H. pylori and intestinal parasitic infections among pregnant women in Okolobri, Bayelsa State. The study highlights the need to screen pregnant women for H. pylori and intestinal parasites to improve antenatal care for both mother and child.

Features of <i>ESCHERICHIA COLI</i> samples from patients with diarrheal syndrome in the Republic of Guinea

Introduction. Diarrheal diseases are a global public health issue and cause 15% of deaths in children under 5 years old, of which about 80% occur in the regions of Africa and Southeast Asia. According to the Global Enteric Multicentre Study (GEMS) conducted in a number of African countries, one of the leading pathogens of high risk of death in infants and young children is diarrheagenic E. coli (DEC). In recent decades, antimicrobial resistance (AMR) has become globally ubiquitous. The Republic of Guinea urgently needs large-scale studies devoted to assessing DEC distribution and antibiotic resistance. The purpose of the study is to assess the pattern of E. coli infections and to test the susceptibility to antibiotics in strains of diarrheagenic E. coli sampled from individuals residing in the Republic of Guinea.
 Materials and methods. From 2019 to 2022, we studied 724 samples of faeces of patients with acute diarrhea, among them 72 (9.9%) children aged 1–5 years, 128 (17.7%) children aged 6–17 years, and 524 (72.4%) people aged 18 years and older; a method of polymerase chain reaction (PCR) was applied with the use of the AmpliSense® Escherichioses-FL reagent kit to identify the genetic determinants of DEC: EPEC, EHEC, ETEC, EIEC, and EAgEC (Central Research Institute of Epidemiology of Rospotrebnadzor, Russia). Susceptibility to 15 antimicrobial agents was found by the disc-diffusion method using Mueller–Hinton agar (Russia) and Oxoid discs (UK). Results were interpreted according EUCAST criteria, versions 2019–2022 (https://www.eucast.org/ast_of_bacteria/previous_versions_of_documents).
 Results. For the period from 2019 to 2022, the percentage of E. coli infections in the etiological pattern of acute intestinal infections amounted to 51.7%. In the age-related manner, DEC was significantly more common in young children aged 0–5 (96.9%, p 0.05) as compared to school age children aged 6–17 (53.9%) and adults (45.6%). In all years of observation, EAgEC strains prevailed, accounting for 38.4%. Other DEC pathotypes, EPEC, ETEC, EIEC and STEC, accounted for 27.2%, 17.5%, 11.8%, and 5.1%, respectively. DEC strains are susceptible to meropenem, amikacin, and nitrofurantoin. The activity of other antibiotics ranged from 11.3% for ampicillin, 28.3% for trimethoprim-sulfamethoxazole, and 34.0% for tetracycline to 73.6% for cephalosporins, 84.0% for aminoglycosides, and 98.1% for fluorinated quinolones.
 Conclusion. To reduce the burden of diarrheal diseases in the Republic of Guinea, it may be necessary to conduct targeted epidemiological and microbiological studies to identify DEC and monitor the development of antimicrobial resistance of E. coli infection pathogens in the population.

Event rates and incidence of post-COVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID)

BackgroundLong-term health outcomes in children and young people (CYP) after COVID-19 infection are not well understood and studies with control groups exposed to other infections are lacking. This study aimed to investigate the incidence of post-COVID-19 condition (PCC) and incomplete recovery in CYP after hospital discharge and compare outcomes between different SARS-CoV-2 variants and non-SARS-CoV-2 infections.MethodsA prospective exposure-stratified cohort study of individuals under 18 years old in Moscow, Russia. Exposed cohorts were paediatric patients admitted with laboratory-confirmed COVID-19 infection between April 2 and December 11, 2020 (Wuhan variant cohort) and between January 12 and February 19, 2022 (Omicron variant cohort). CYP admitted with respiratory and intestinal infections, but negative lateral flow rapid diagnostic test and PCR-test results for SARS-CoV-2, between January 12 and February 19, 2022, served as unexposed reference cohort. Comparison between the ‘exposed cohorts’ and ‘reference cohort’ was conducted using 1:1 matching by age and sex. Follow-up data were collected via telephone interviews with parents, utilising the long COVID paediatric protocol and survey developed by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The WHO case definition was used to categorise PCC.ResultsOf 2595 CYP with confirmed COVID-19, 1707 (65.7%) participated in follow-up interviews, with 1183/1707 (69%) included in the final ‘matched’ analysis. The median follow-up time post-discharge was 6.7 months. The incidence of PCC was significantly higher in the Wuhan variant cohort (89.7 cases per 1000 person-months, 95% CI 64.3–120.3) compared to post-infection sequalae in the reference cohort (12.2 cases per 1000 person-months, 95% CI 4.9–21.9), whereas the difference with the Omicron variant cohort and reference cohort was not significant. The Wuhan cohort had higher incidence rates of dermatological, fatigue, gastrointestinal, sensory, and sleep manifestations, as well as behavioural and emotional problems than the reference cohort. The only significant difference between Omicron variant cohort and reference cohort was decreased school attendance. When comparing the Wuhan and Omicron variant cohorts, higher incidence of PCC and event rates of fatigue, decreased physical activity, and deterioration of relationships was observed. The rate of incomplete recovery was also significantly higher in the Wuhan variant cohort than in both the reference and the Omicron variant cohorts.ConclusionsWuhan variant exhibited a propensity for inducing a broad spectrum of physical symptoms and emotional behavioural changes, suggesting a pronounced impact on long-term health outcomes. Conversely, the Omicron variant resulted in fewer post-infection effects no different from common seasonal viral illnesses. This may mean that the Omicron variant and subsequent variants might not lead to the same level of long-term health consequences as earlier variants.

Deworming coverage and its determinants among 12-59 months old children in East Africa: A population-based study.

Intestinal parasitic infections are the world's largest public health issue, primarily in developing nations. The World Health Organization (WHO) recommends deworming as a preventative or therapeutic measure for all vulnerable people residing in endemic areas. Despite this issue, there is little data on the prevalence and associated factors of deworming drug use among children under five years of age in East Africa. This study aimed to evaluate the prevalence and contributing factors of deworming coverage among children under the age of five in East Africa using the most available national health survey data. Data from the Demographic and Health Survey, which included 103,865 weighted children between the ages of 12-59 months, were used in this investigation. Our outcome of interest was taking deworming medicine six months before the interview. A logistic regression model was then fitted. A cutoff P value of 0.2 was used in the binary logistic regression analysis. To identify significant variables, a 95% confidence interval and adjusted odds ratio (AOR) with a value < 0.05 were used. The prevalence of deworming in East Africa was 54.13% (95% CI: 53.83%-54.43%). The maternal age group of 24-34 years, and from 35-49 years (AOR = 1.37, 95% CI, 1.32,1.42), and (AOR = 1.71, 95% CI, 1.62,1.79), employed women (AOR = 1.62, 95% CI, 1.58,1.67), being from rural(AOR = 1.11,95% CI,1.07,1.15), unmarried mothers (AOR = 1.12,95% CI,1.09,1.15), mothers from poorer, middle, richer, and richest households (AOR = 1.16,95% CI, 1.12,1.21), (AOR = 1.23, 95% CI, 1.18,1.28), (AOR = 1.22,95% CI, 1.16,1.27), and (AOR = 1.27, 95% CI, 1.21,1.34) having at least one antenatal care follow up(AOR = 2.90, 95% CI, 2.63,3.16), health facility delivery(AOR = 1.69, 95% CI,1.64,1.75), mass media exposure AOR = 1.32, 955 CI, 1.29,1.36), having of 3-5 children (AOR = 0.89, 95% CI, 0.86,0.93), more than five children (AOR = 0.79, 95% CI, 0.73,0.86), and parity of 2nd or 3rd birth order (AOR = 1.05, 95% CI, 1.01,1.09) as compared to primi mothers were associated with the deworming among under five children in east Africa respectively. The under-five population in East Africa had a lower prevalence of deworming medication per the most recent DHS findings. Promoting mother and child health services (antenatal care, institutional delivery, family planning), as well as women's empowerment, should be prioritized.

Effects of myeloperoxidase on inflammatory responses with hypoxia in Citrobacter rodentium-infectious mice.

Myeloperoxidase (MPO)has been identified as a mediator in various inflammatory diseases. Bacterial infection of the intestine and hypoxia can both lead to inflammatory responses, but the role of MPO in these phenomena remains unclear. By building the MPO-/- mice, we evaluated relevant inflammatory factors and tissue damage in mice with intestinal Citrobacter rodentium infection and hypoxia. The body weight and excreted microorganisms were monitored. Intestinal tissues were collected 7 days after bacterial infection under hypoxia to undergo haematoxylin-eosin staining and assess the degree of pathological damage. ELISA assays were performed to quantify the serum levels of TNF-α, IFN-γ, IL-6, and IL-1β inflammatory cytokines. PCR, WB, and IF assays were conducted to determine the expression of chemokines MCP1, MIP2, and KC in the colon and spleen. The C. rodentium infection and hypoxia caused weight loss, intestinal colitis, and splenic inflammatory cells active proliferation in wild-type mice. MPO deficiency alleviated this phenomenon. MPO-/- mice also displayed a significant decline in bacteria clearing ability. The level of TNF-α in the serum and spleen was both lower in MPO-/- hypoxia C. rodentium-infected mice than that in wild-type mice. The chemokines expression levels of MIP2, KC,and MCP1 in the spleen and colon of each bacterial infected group were significantly increased (p < .05), while in hypoxia, the factors in the spleen and colon were decreased (p < .05). MPO deficiency was found to lower the levels of these chemokines compared with wild-type mice. MPO plays an important role of the inflammatory responses in infectious enteritis and hypoxia in mice, and the loss of MPO may greatly reduce the body's inflammatory responses to fight diseases.

Host-gut microbiota interactions shape parasite infections in farmed Atlantic salmon.

Animals and their associated microbiota share long evolutionary histories. However, it is not always clear how host genotype and microbiota interact to affect phenotype. We applied a hologenomic approach to explore how host-microbiota interactions shape lifetime growth and parasite infection in farmed Atlantic salmon (Salmo salar). Multi-omics data sets were generated from the guts of 460 salmon, 82% of which were naturally infected with an intestinal cestode. A single Mycoplasma bacterial strain, MAG01, dominated the gut metagenome of large, non-parasitized fish, consistent with previous studies showing high levels of Mycoplasma in the gut microbiota of healthy salmon. While small and/or parasitized salmon also had high abundance of MAG01, we observed increased alpha diversity in these individuals, driven by increased frequency of low-abundance Vibrionaceae and other Mycoplasma species that carried known virulence genes. Colonization by one of these cestode-associated Mycoplasma strains was associated with host individual genomic variation in long non-coding RNAs. Integrating the multi-omic data sets revealed coordinated changes in the salmon gut mRNA transcriptome and metabolome that correlated with shifts in the microbiota of smaller, parasitized fish. Our results suggest that the gut microbiota of small and/or parasitized fish is in a state of dysbiosis that partly depends on the host genotype, highlighting the value of using a hologenomic approach to incorporate the microbiota into the study of host-parasite dynamics.IMPORTANCEStudying host-microbiota interactions through the perspective of the hologenome is gaining interest across all life sciences. Intestinal parasite infections are a huge burden on human and animal health; however, there are few studies investigating the role of the hologenome during parasite infections. We address this gap in the largest multi-omics fish microbiota study to date using natural cestode infection of farmed Atlantic salmon. We find a clear association between cestode infection, salmon lifetime growth, and perturbation of the salmon gut microbiota. Furthermore, we provide the first evidence that the genetic background of the host may partly determine how the gut microbiota changes during parasite-associated dysbiosis. Our study therefore highlights the value of a hologenomic approach for gaining a more in-depth understanding of parasitism.

Entamoeba histolytica Infection in the Philippines: A Review

Entamoeba histolytica, an intestinal protozoan parasite, is the primary causative agent of both intestinal and extraintestinal amoebiasis. While six species of Entamoeba have been identified in the human gut, only E. histolytica is well recognized as a pathogenic amoeba associated with intestinal and extraintestinal infections. In many cases of E. histolytica infection, symptoms are either absent or mild, whereas the most frequent clinical manifestations are colitis and liver abscess due to amoebic infection. Diagnosis typically relies on microscopic and serological methods. Metronidazole is the standard therapy for treating children and adults with invasive amoebiasis. However, the absence of an effective vaccine poses a significant challenge to controlling the transmission and progression of the parasite into an active, invasive disease. Notably, in developing tropical countries like the Philippines, significant cases of E. histolytica infections have been documented in communities with inadequate sanitation and hygiene practices. The development of pragmatic and cost-effective diagnostic methods is therefore crucial for the clinical care of amoebiasis patients. Drawing from a limited pool of published articles (2010 to date) on cases of E. histolytica infections and parasitological surveys in the Philippines, the current review underscores the critical knowledge gap on the prevalence of amoebiasis as well as the disease pathology and treatment of this zoonotic parasitic disease.

Reviewing the Clostridioides difficile Mouse Model: Insights into Infection Mechanisms.

Clostridioides difficile is an anaerobic, spore-forming bacterium associated with intestinal infection, manifesting a broad spectrum of gastrointestinal symptoms, ranging from mild diarrhea to severe colitis. A primary risk factor for the development of C. difficile infection (CDI) is antibiotic exposure. Elderly and immunocompromised individuals are particularly vulnerable to CDI. A pivotal aspect for comprehending the complexities of this infection relies on the utilization of experimental models that mimic human CDI transmission, pathogenesis, and progression. These models offer invaluable insights into host-pathogen interactions and disease dynamics, and serve as essential tools for testing potential therapeutic approaches. In this review, we examine the animal model for CDI and delineate the stages of infection, with a specific focus on mice. Our objective is to offer an updated description of experimental models employed in the study of CDI, emphasizing both their strengths and limitations.

Effects of public health interventions and zero COVID policy on paediatric diseases: A Southern China study.

With the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in schools and communities, clinical evidence is needed to determine the impact of the pandemic and public health interventions under the zero coronavirus disease policy on the occurrence of common infectious diseases and non-infectious diseases among children. The current study was designed to analyse the occurrence of common infectious diseases before and after the pandemic outbreak in southern China. Data was obtained for 1 801 728 patients admitted into children's hospitals in Guangzhou between January 2017 and July 2022. Regression analysis was performed for data analysis. The annual occurrence of common paediatric infectious diseases remarkably decreased after the pandemic compared to the baseline before the pandemic and the monthly occurrence. Cases per month of common paediatric infectious diseases were significantly lower in five periods during the local outbreak when enhanced public health measures were in place. Cases of acute non-infectious diseases such as bone fractures were not reduced. Non-pharmaceutical interventions decreased annual and monthly cases of paediatric respiratory and intestinal infections during the coronavirus disease 2019 (COVID-19) pandemic, especially when enhanced public health interventions were in place. Our findings provide clinical evidence that public health interventions under the dynamic zero COVID policy in the past three years had significant impacts on the occurrence of common respiratory and intestinal infectious diseases among children and adolescents but little impact on reducing non-infectious diseases such as leukaemia and bone fracture.

Prevalence of intestinal parasites and comparison of detection techniques for soil-transmitted helminths among newly arrived expatriate labors in Jeddah, Saudi Arabia.

Diversity in clinical signs and symptoms are associated with soil transmitted diseases (STD), which are spread to humans by intestinal worms and transmitted in a variety of ways. There is a need for the present study, which aimed to investigate the prevalence of intestinal parasites and to compare between the common detection techniques for soil-transmitted helminths (STHs) among newly arrived expatriate labors in Jeddah, Saudi Arabia. A total of 188 stool samples were analyzed by macroscopic examination, and microscopic examination using direct iodine smear and the formal ether sedimentation technique. Trichrome and modified Kinyoun's stains were used to confirm the morphology of any detected protozoa stages and oocyst of Cryptosporidium, respectively. A chromatographic immunoassay kit was used for Entamoeba histolytica, Giardia lamblia and Cryptosporidium. In addition, real-time PCR was employed only to identify various STHs. Out of 188, several types of parasites were detected in 35 samples (18.62%), of which some with multiple infections. Nine samples (4.79%) were positive for Entamoeba coli, seven samples (3.72%) for Trichuris trichiura, six samples (3.19%) for Necator americanus, four samples (2.13%) for Strongyloides stercoralis, four samples (2.13%) for Ascaris lumbricoides, four samples (2.13%) for E. histolytica, three samples (1.60%) for Blastocystis hominis and two samples (1.06%) for Ancylostoma duodenale. In comparison between laboratory techniques for STHs, real-time PCR was able to detect the DNA of 19 samples (10.1%) followed by Ritchie sedimentation technique (18, 9.6%), and direct smear (7, 3.7%) (p > 0.05). The high rate of newly arrived foreign workers infected with intestinal parasites could lead to a risk to society. Continuous and regular surveys are needed to deal with the occurrence of intestinal parasitic infections including STHs. To improve the identification of these infections, we recommend a supporting infrastructure for the application of concentration methods and molecular assays.

In vitro evaluation of the immunomodulatory and wakame assimilation properties of Lactiplantibacillus plantarum strains from swine milk.

The emergence and spread of antibiotic resistance threat forced to explore alternative strategies for improving the resistance to pathogens in livestock production. Probiotic lactic acid bacteria represent an alternative for this objective. In this study, seven Lactiplantibacillus plantarum strains from porcine colostrum and milk were isolated, identified and characterized in terms of their abilities to modulate immunity in porcine intestinal epithelial (PIE) cells. Then, two potential immunoregulatory strains were studied in terms of their ability to utilize and grow in wakame (Undaria pinnafida). Isolates were identified by 16S rRNA gene and evaluated by studying their interaction with PIE cells. The expressions of peptidoglycan recognition proteins (PGRPs), nucleotide-binding oligomerization domain (NODs), host defense peptides (pBD), and type I interferons (IFNs) were evaluated by RT-qPCR. The strain 4M4417 showed a remarkable capacity to differentially regulate the expression of PGRP1, PGRP3, NOD1, NOD2, and pBD1 in PIE cells. On the other hand, the strain 4M4326 was the most efficient to improve the expression of IFN-α and IFN-β in PIE cells challenged with poly (I:C). Both L. plantarum 4M4326 and 4M4417 were characterized in terms of their ability to utilize wakame. Results demonstrated that both strains efficiently grew in wakame-based broth. Our results suggest that L. planatrum 4M4326 and 4M4417 are interesting candidates to develop immunomodulatory feeds based on wakame utilization. These new immunosynbiotic feeds could help to reduce severity of intestinal infections and improve immune health status in pigs.

GROUP 3 INNATE LYMPHOID CELLS RELY ON ER STRESS RESPONSE FOR CYTOKINE PRODUCTION IN IBD

Abstract BACKGROUNDS Group 3 innate lymphoid cells (ILC3s) recently emerged as important regulators and potential drug targets for IBD. However, the response of ILC3s to environmental stimuli during intestinal inflammation remains elusive. IRE1a-XBP1 serves as the regulatory hub of the endoplasmic reticulum stress response that plays a vital role in intestinal inflammation. METHODS We generated conditional knockout Ire1aflo/flox,Rorc-Cre (Ire1aΔRorc) and Rag-/-Ire1aΔRorc mice with Ire1a deleted in ILC3s. Intestinal infections were induced by Citrobacter rodentium and Clostridium difficile. ILC3s-derived cytokines including IL-22 is crucial for host defense in the acute phase of C. rodentium and C. difficile infection. Dextran sodium sulfate (DSS) was given in drinking water to induce acute colitis. We recruited patients with active Crohn’s disease (CD) and collected ileal biopsies during routine colonoscopy before starting ustekinumab, a non-selective anti-IL-23 antibody. Mucosal ILC3s were isolated for analysis of ILC3s by flow cytometry. RESULTS In murine intestinal ILC3s, the activity of IRE1a-XBP1 pathway follows a robust 24h circadian rhythm which parallels that of clock genes and cytokines including IL-22. XBP1s is activated in ILC3s ex vivo by vasoactive intestinal peptide, which was previous shown to orchestrate the circadian expression of IL-22 by ILC3s. IRE1a-XBP1 in intestinal ILC3s is further activated in response to IL-23 and colitis in mice, as well as in inflamed IBD tissues compared to normal tissues from healthy individuals. We further showed that IRE1a-XBP1 activation in stimulated ILC3s requires mitochondrial reactive oxygen species (mtROS) (Fig 1). Using the Ire1aΔRorc mice, we demonstrated that IRE1a-XBP1 is critical for cytokine expression by ILC3s. Ire1aΔRorc mice are highly susceptible to acute C. rodentium and C. difficile infection as well as acute DSS colitis (similar vulnerabilities were found in Rag-/-Ire1aΔRorc mice compared to Rag-/-Ire1aflox/flox littermates). Ire1aΔRorc mice exhibit reduced IL-22 and IL-17A in ILC3s and impaired epithelial barrier function with diminished expression of mucins and antimicrobial peptides. The susceptibilities of Ire1aΔRorc and Rag-/-Ire1aΔRorc mice to colitis were rescued by administration of recombinant IL-22 (Fig 2). Moreover, the frequency of XBP1s+ ILC3s in ileal mucosa from CD patients before initiation of ustekinumab positively correlates with response to therapy. CONCLUSIONS We demonstrate that a non-canonical mtROS-IRE1a-XBP1 pathway augments cytokine production by intestinal ILC3s. Loss of IRE1a-XBP1 in ILC3s impairs the optimal and rhythmic expression of protective cytokines and renders the mice more susceptible to intestinal infections and colitis. We also identify XBP1+ ILC3s as a potential biomarker for predicting responsiveness to anti-IL-23 therapies in IBD.

DOP89 Unfolded protein response controls group 3 innate lymphoid cells in IBD

Abstract Background Group 3 innate lymphoid cells (ILC3s) have recently emerged as important regulators and potential drug targets for IBD. However, the response of ILC3s to environmental stimuli during intestinal inflammation remains elusive. IRE1a-XBP1 serves as the regulatory hub of endoplasmic reticulum stress and the unfolded protein response (UPR) that plays a vital role in intestinal inflammation. Methods We generated conditional knockout Ire1aflo/flox,Rorc-Cre (Ire1aΔRorc) and Rag-/-Ire1aΔRorc mice with Ire1a deleted in ILC3s. Intestinal infections were induced by Citrobacter rodentium and Clostridium difficile. ILC3s-derived cytokines including IL-22 is crucial for host defense in the acute phase of C. rodentium and C. difficile infection. Dextran sodium sulfate (DSS) was given in drinking water to induce acute colitis. We recruited patients with active Crohn’s disease (CD) and collected ileal biopsies during routine colonoscopy before starting ustekinumab, a non-selective anti-IL-23 antibody. Mucosal ILC3s were isolated for analysis of ILC3s by flow cytometry. Results In murine intestinal ILC3s, the activity of IRE1a-XBP1 pathway follows a robust 24h circadian rhythm which parallels that of clock genes and cytokines including IL-22. XBP1s is activated in ILC3s ex vivo by vasoactive intestinal peptide, which was previous shown to orchestrate the circadian expression of IL-22 by ILC3s. IRE1a-XBP1 in intestinal ILC3s is further activated in response to IL-23 and colitis in mice, as well as in inflamed IBD tissues compared to normal tissues from healthy individuals. We further showed that IRE1a-XBP1 activation in stimulated ILC3s requires mitochondrial reactive oxygen species (mtROS) (Fig 1). Using the Ire1aΔRorc mice, we demonstrated that IRE1a-XBP1 is critical for cytokine expression by ILC3s. Ire1aΔRorc mice are highly susceptible to acute C. rodentium and C. difficile infection as well as acute DSS colitis (similar vulnerabilities were found in Rag-/-Ire1aΔRorc mice compared to Rag-/-Ire1aflox/flox littermates). Ire1aΔRorc mice exhibit reduced IL-22 and IL-17A in ILC3s and impaired epithelial barrier function with diminished expression of mucins and antimicrobial peptides. The susceptibilities of Ire1aΔRorc and Rag-/-Ire1aΔRorc mice to colitis were rescued by administration of recombinant IL-22 (Fig 2). Moreover, the frequency of XBP1s+ ILC3s in ileal mucosa from CD patients before initiation of ustekinumab positively correlates with response to therapy. Conclusion We demonstrate that a non-canonical mtROS-IRE1a-XBP1 pathway augments cytokine production by intestinal ILC3s. We also identify XBP1+ ILC3s as a potential biomarker for predicting responsiveness to anti-IL-23 therapies in IBD.

Intestinal Helminths Infections as Infrequent Cause of Emergency Abdominal Surgery: A Retrospective Study in a University Hospital over 20 Years.

All organs of any organism can be affected by helminths. They can be seen in a broad spectrum, from simple infestations to extensive, life-threatening involvement. Symptomatology is usually of chronic latent course. However, sometimes the presentation is acute and requires urgent surgical intervention. We conducted a retrospective observational prospective recruitment study of patients undergoing emergency surgery for helminth infection from January 2000 to December 2019 at a university hospital. Sociodemographic and analytical variables, variables related to the clinical process, and the diagnostic test were analysed. Variables related to the surgical procedure and postoperative complications were also analysed. A total of 36 patients required emergency surgery for their helminth infection, which represented 0.26% of emergency abdominal surgeries. The mean age was 34.91 ± 21.5 years, with a predominance of men (69.4%). Most patients presented with pain in the right iliac fossa (69.4%), followed by symptoms compatible with intestinal obstruction (19.4%). The most frequent surgical interventions were appendectomy (38.9%) followed bowel resection (33.3%) and ileocecal resection (11.1%). Enterobious vermicularis and Anisakis simplex both together accounted for 75% of the sample. Statistically significant differences were identified in age (p < 0.001), diagnostic test performed (p = 0.032), intraoperative clinical diagnosis (p = 0.005) and surgical treatment received (p < 0.001). The frequency of emergency surgeries for intestinal helminth parasitism is decreasing. However, the majority of these are E. vermicularis and Anisakis simplex, which have distinctly different clinical presentations. Identification and recognition by physicians continue to be necessary for further postoperative management and possible complications.

Exploring the predictive power of jejunal microbiome composition in clinical and subclinical necrotic enteritis caused by Clostridium perfringens: insights from a broiler chicken model

BackgroundNecrotic enteritis (NE) is a severe intestinal infection that affects both humans and poultry. It is caused by the bacterium Clostridium perfringens (CP), but the precise mechanisms underlying the disease pathogenesis remain elusive. This study aims to develop an NE broiler chicken model, explore the impact of the microbiome on NE pathogenesis, and study the virulence of CP isolates with different toxin gene combinations.MethodsThis study established an animal disease model for NE in broiler chickens. The methodology encompassed inducing abrupt protein changes and immunosuppression in the first experiment, and in the second, challenging chickens with CP isolates containing various toxin genes. NE was evaluated through gross and histopathological scoring of the jejunum. Subsequently, jejunal contents were collected from these birds for microbiome analysis via 16S rRNA amplicon sequencing, followed by sequence analysis to investigate microbial diversity and abundance, employing different bioinformatic approaches.ResultsOur findings reveal that CP infection, combined with an abrupt increase in dietary protein concentration and/or infection with the immunosuppressive variant infectious bursal disease virus (vIBDV), predisposed birds to NE development. We observed a significant decrease (p < 0.0001) in the abundance of Lactobacillus and Romboutsia genera in the jejunum, accompanied by a notable increase (p < 0.0001) in Clostridium and Escherichia. Jejunal microbial dysbiosis and severe NE lesions were particularly evident in birds infected with CP isolates containing cpa, netB, tpeL, and cpb2 toxin genes, compared to CP isolates with other toxin gene combinations. Notably, birds that did not develop clinical or subclinical NE following CP infection exhibited a significantly higher (p < 0.0001) level of Romboutsia. These findings shed light on the complex interplay between CP infection, the gut microbiome, and NE pathogenesis in broiler chickens.ConclusionOur study establishes that dysbiosis within the jejunal microbiome serves as a reliable biomarker for detecting subclinical and clinical NE in broiler chicken models. Additionally, we identify the potential of the genera Romboutsia and Lactobacillus as promising candidates for probiotic development, offering effective alternatives to antibiotics in NE prevention and control.

Clinical and epidemiological features of ulcerative colitis in children of the Rostov region

Russian data on the prevalence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC), confirm the general global trend towards an increase in IBD, taking into account age-related as well as regional characteristics, which determined the purpose of this study. The purpose of the study. To evaluate the clinical and epidemiological features of the course of ulcerative colitis in children of Rostov-on-Don. Materials and methods. We observed 42 children aged from 1 to 14 years with a diagnosis of UC, which was made on the basis of anamnesis, clinical picture, laboratory test results, colonoscopy data, and morphological examination of the colon mucosa. UC activity was assessed taking into account the PUCAI index. Results. For the period from 2014 to 2023 On the basis of the pediatric somatic department of city hospital No. 20 in Rostov-on-Don, UC was diagnosed in 42 children aged 1 to 14 years, which amounted to 1.48% of the total number of patients with chronic intestinal diseases (2822 people). There was an increase in the incidence of ulcerative colitis from 2014 to 2023 (from 0.32% to 2.52%) with maximum values in 2021-2023. Conclusion. Clinical and epidemiological studies have shown an increase in the incidence of UC in children of Rostov-on-Don over the past 10 years. It has been established that ulcerative colitis is more often detected in the preschool group of children. The incidence of ulcerative colitis was higher in boys than in girls. A high degree of family history of children with UC was revealed for diseases of the digestive system, delivery by Caesarean section, artificial feeding in the first year of life, and acute intestinal infections. In the UC clinic, milder, erased forms of the disease dominated, which determined the later diagnosis of the disease at the prehospital stage.

Description of Characteristics of Typhoid Fever Sufferers in Children Aged 5-14 Years at RSU Royal Prima Medan for the Period August 2022-February 2023

Infectious diseases are still a public health problem, especially in developing countries. One of the infectious diseases is typhoid fever. Typhoid fever is an acute infection of the small intestine with symptoms of fever lasting more than one week, which can cause digestive disorders and reduce the level of consciousness. This research aims to analyze the characteristics of typhoid fever sufferers in children aged 5-14 years at RSU Royal Prima Medan from August 2022 - February 2023. The type of research used in this research is a qualitative description with a cross-sectional design. The population used was 46 medical records of typhoid fever sufferers in children aged 5-14 years at RSU Royal Prima Medan from August 2022 - February 2023. The sampling technique used in this research used total sampling, while the number of samples used was 46 records. Medical treatment for typhoid fever patients. Data analysis uses univariate analysis. The results of the study showed that the number of typhoid fever sufferers in children aged 5-14 years at RSU Royal Prima Medan from August 2022 – February 2023 was 46 children, 27 of the sufferers were predominantly male while 19 were female. All typhoid fever sufferers in this study experienced accompanying symptoms of fever, nausea, vomiting, and diarrhea; only five typhoid fever sufferers, or 10.9%, were accompanied by additional accompanying symptoms in the form of abdominal pain. Normal body weight in male patients was 19 patients, and abnormal body weight was eight patients. Normal body weight in female patients was eight patients, and abnormal body weight was 11 patients. All typhoid fever sufferers received RL and NaCL therapy, only 11 sufferers received additional Cefixime therapy, and only 32 sufferers received additional Cefriaxone therapy. August 2022 – February 2023 is &gt; 3 days.

MicroRNA expression profile of chicken jejunum in different time points Eimeria maxima infection.

Coccidiosis stands as a protozoan disease of notable economic impact, characterized by an intracellular parasite that exerts substantial influence over poultry production. This invasion disrupts the integrity of the enteric mucosa, leading to the emergence of severe lesions and diminishing the efficiency of feed utilization in chickens. MicroRNA (miRNA) are short, non-coding RNA molecules with approximately 21-24 nucleotides long in size that play essential roles in various infectious diseases and inflammatory responses. However, the miRNA's expression patterns and roles in the context of Eimeria maxima infection of chicken intestines remain unclear. miRNA sequencing was employed to assess the miRNA expression profile in chicken jejunum during E. maxima infection. In this study, we analyzed miRNA expression profiles related to the host's immune response in the chicken jejunum during E. maxima infection. At 4 days infection and control (J4I versus J4C), 21 differentially expressed miRNAs in the jejunum were identified, comprising 9 upregulated and 12 downregulated miRNAs. Furthermore, in the jejunum, at 7 days infection and control (J7I versus J7C) groups, a total of 35 significantly differentially expressed miRNAs were observed, with 13 upregulated and 22 downregulated miRNAs. The regulatory networks were constructed between differentially expressed miRNA and mRNAs to offer insight into the interaction mechanisms between chickens and E. maxima coccidian infection. Furthermore, within the comparison group, we obtained 946, 897, and 281 GO terms that exhibited significant enrichment associated with host immunity in the following scenarios, J4I vs. J4C, J7I vs. J7C, and J4I vs. J7I, respectively. The KEGG pathway analysis indicated notable enrichment of differentially expressed miRNAs in the jejunum, particularly in J4I vs. J4C; enriched pathways included metabolic pathways, endocytosis, MAPK signaling pathway, regulation of actin cytoskeleton, and cytokine-cytokine receptor interaction. Moreover, in J7I vs. J7C, the KEGG pathway was significantly enriched, including metabolic pathways, protein processing in the endoplasmic reticulum, ubiquitin-mediated proteolysis, and FoxO signaling pathway. A comprehensive understanding of the host genetic basis of resistance with a combination of time-dependent infection to the Eimeria parasite is crucial for pinpointing resistance biomarkers for poultry production.

Immunogenicity and efficacy of an oral live-attenuated vaccine for bovine Johne's disease.

Mycobacterium avium subsp. paratuberculosis (MAP), the etiological agent of Johne's disease (JD) in ruminants, establishes a prolonged and often lifelong enteric infection. The implementation of control measures for bovine JD has faced obstacles due to the considerable expenses involved in disease surveillance and hindered by unreliable and inadequate diagnostic tests, emphasizing the need for an effective vaccine that can stimulate mucosal immunity in the gastrointestinal tract. Previous investigations have demonstrated that deletion of the BacA gene in MAP produces an attenuated strain that can transiently colonize the calf small intestine while retaining its capacity to stimulate systemic immune responses similar to wildtype MAP strains. This study assessed the efficacy of the BacA gene deletion MAP strain, referred to as the BacA vaccine, when administered orally to young calves. The research aimed to evaluate its effectiveness in controlling MAP intestinal infection and to investigate the immune responses elicited by mucosal vaccination. The study represents the first evaluation of an enteric modified live MAP vaccine in the context of an oral MAP challenge in young calves. Oral immunization with BacA reduced MAP colonization specifically in the ileum and ileocecal valve. This partially protective immune response was associated with an increased frequency of CD4+ and CD8+ T cells with a pro-inflammatory phenotype (IFNγ+/TNFα+) in vaccinated animals. Moreover, re-stimulated PBMCs from vaccinated animals showed increased expression of IFNγ, IP-10, IL-2, and IL-17 at 10- and 12-weeks post challenge. Furthermore, immunophenotyping of blood leukocytes revealed that vaccinated calves had increased levels of T cells expressing cell-surface markers consistent with long-term central memory. Overall, our findings provide new insights into the development and immunogenicity of a modified live MAP vaccine against bovine JD, demonstrating oral vaccination can stimulate host immune responses that can be protective against enteric MAP infection.