Host Intestinal Tissues Research Articles

Successful Clinical Avoidance of Colorectal Anastomotic Leakage through Local Decontamination.

An anastomotic leak is an unpredictable postoperative complication during recovery from colorectal surgery that may require a re-operation. Potentially pathogenic bacteria like Pseudomonas (and Enterococcus) contribute to the pathogenesis of an anastomotic leak through their capacity to degrade collagen and to activate tissue matrix metalloprotease-9 in host intestinal tissues. The microbiome, therefore, is the key to preventing an anastomotic leak after colorectal surgery. The aim of this trial was to investigate whether perioperative selective decontamination with a new mixture of locally acting antibiotics specially designed against Pseudomonas aeruginosa and Enterococcus faecalis can reduce or even stop early symptomatic leakage. All hospitalized patients in our University Clinic undergoing colorectal surgery with a left-sided anastomosis were included as two groups; patients in the intervention group received polymyxin B, gentamicin and vancomycin every six hours for five postoperative days and those in the control group did not receive such an intervention. An anastomotic leak was defined as a clinically obvious defect of the intestinal wall integrity at the colorectal anastomosis site (including suture) that leads to a communication between the intra- and extraluminal compartments, requiring a re-do surgery within seven postoperative days. Between February 2017 and May 2023, a total of 301 patients (median age of 63 years) were analyzed. An anastomotic leak was observed in 11 patients in the control group (n = 152), but in no patients in the intervention group (n = 149); this difference was highly significant. The antibiotic mixture (with polymyxin B, gentamicin and vancomycin) used for local decontamination in our study stopped the occurrence of anastomotic leaks completely. According to the definition of anastomotic leak, no further surgery was required after local perioperative decontamination.

Stigmasterol: Remodeling gut microbiota and suppressing tumor growth through Treg and CD8+ T cells in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC), the most primary malignant liver tumor and is ranked as the fifth most common malignancy worldwide. Despite various therapeutic approaches being used in clinical practice, the overall effectiveness remains insufficient. Stigmasterol, a compound known for its anti-tumor properties and ability to induce apoptosis in tumor cells, has been found to influenced the composition of the intestinal microbiota. However, the mechanism through which stigmasterol influences the intestinal microbial-host crosstalk in HCC remains elusive. PurposeThis study was to investigate whether stigmasterol can remodel gut microbiota, and suppress tumor volume by regulating Treg and IFN-γ+ CD8+ cell in the host with HCC. MethodStigmasterol (at dosages of 0, 50, 100, or 200 mg/kg) was orally administered to Balb/c mice with subcutaneous tumor once every 2 days for 3 weeks. ResultsWe first found that tumors volume in the group treated with 100 mg/kg stigmasterol were significantly decreased compared with those in the control group (P < 0.05), which exhibited a similar effect as the sorafenib treatment in mice with HCC. This resulted in a significant upregulation of Caspase3, Bax, and P53 expressions, as well as a decrease in Cyclin D1 expression, ultimately leading to a reduction in tumor volume. Additionally, stigmasterol can alter the α and β diversity of the intestinal flora and significantly increase the abundance of Lactobacillus_johnsonii, Lactobacillus_murinus, and Lactobacillus_reuteri (P<0.05), which can lead to a decrease in the ratio of regulatory T cells (Tregs) to CD8+ T cells in the intestinal tract and tumor tissue, and consequently enhance immune response in the tumor microenvironment (TME) in the host with HCC. ConclusionIn this study, we initially utilized different dosages of stigmasterol to intervene in mice with HCC and confirmed its inhibitory effects on tumor growth in vivo, and discovered that stigmasterol affected Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri, resulting in an increased proportion of IFN-γ+ CD8+ T cells and Treg cells in both the intestinal mucosa and tumor tissues, and ultimately leading to increased levels of apoptotic proteins and the subsequent death of tumor cells, which shed light on the effect of stigmasterol on host intestinal tissue and intratumoral immune cells by reshaping the intestinal microbiota, and provide a theoretical foundation for the potential clinical application of stigmasterol in the treatment of HCC.

Potential mechanism of pyrotinib-induced diarrhea was explored by gut microbiome and ileum metabolomics.

Pyrotinib is a novel epidermal growth factor receptor/human epidermal growth factor receptor-2 (HER2) tyrosine kinase inhibitor that exhibited clinical efficacy in patients with HER2-positive breast cancer and HER2-mutant/amplified lung cancer. However, severe diarrhea adverse responses preclude its practical use. At present, the mechanism of pyrotinib-induced diarrhea is unknown and needs further study. First, to develop a suitable and reproducible animal model, we compared the effects of different doses of pyrotinib (20, 40, 60 and 80 mg/kg) in Wistar rats. Second, we used this model to examine the intestinal toxicity of pyrotinib. Finally, the mechanism underlying pyrotinib-induced diarrhea was fully studied using gut microbiome and host intestinal tissue metabolomics profiling. Reproducible diarrhea occurred in rats when they were given an 80 mg/kg daily dose of pyrotinib. Using the pyrotinib-induced model, we observed that Lachnospiraceae and Acidaminococcaceae decreased in the pyrotinib groups, whereas Enterobacteriaceae, Helicobacteraceae and Clostridiaceae increased at the family level by 16S rRNA gene sequence. Multiple bioinformatics methods revealed that glycocholic acid, ursodeoxycholic acid and cyclic AMP increased in the pyrotinib groups, whereas kynurenic acid decreased, which may be related to the pathogenesis of pyrotinib-induced diarrhea. Additionally, pyrotinib-induced diarrhea may be associated with a number of metabolic changes mediated by the gut microbiome, such as Primary bile acid biosynthesis. We reported the establishment of a reproducible pyrotinib-induced animal model for the first time. Furthermore, we concluded from this experiment that gut microbiome imbalance and changes in related metabolites are significant contributors to pyrotinib-induced diarrhea.

Biochemical contents of Cotylophoron cotylophorum (Fischoeder, 1901) stiles et Goldberger, 1910 and its host intestinal tissue

Biochemical contents of Cotylophoron cotylophorum (Fischoeder, 1901) stiles et Goldberger, 1910 and its host intestinal tissue

Hand Dissection of Caenorhabditis elegans Intestines.

Comprised of only 20 cells, the Caenorhabditis elegans intestineis the nexus of many life-supporting functions, including digestion, metabolism, aging, immunity, and environmental response. Critical interactions between the C. elegans host and its environment converge within the intestine, where gut microbiota concentrate. Therefore, the ability to isolate intestine tissue away from the rest of the worm is necessary to assess intestine-specific processes. This protocol describes a method for hand dissecting adult C. elegans intestines. The procedure can be performed in fluorescently labeled strains for ease or training purposes. Once the technique is perfected, intestines can be collected from unlabeled worms of any genotype. This microdissection approach allows for the simultaneous capture of host intestinal tissue and gut microbiota, a benefit to many microbiome studies. As such, downstream applications for the intestinal preparations generated by this protocol can include but are not limited to RNA isolation from intestinal cells and DNA isolation from captured microbiota. Overall, hand dissection of C. elegans intestines affords a simple and robust method to investigate critical aspects of intestine biology.

STUDY OF BIOCHEMICAL COMPONENTS OF CESTODE PARASITES FROM Capra hircus (L) IN SOLAPUR DISTRICT (M.S), INDIA

In biochemistry, the study of biomolecules such as proteins, glycogen and lipids, are very important in each and every organism. A cestode parasite absorbs all nutritive biomolecules from the body host. In the present study cestode parasites, infected intestine and non-infected intestine of the host are determined by biomolecules such as protein, glycogen, and lipid. The estimation of protein content in the cestode parasites and host intestinal tissue (infected and non-infected) were carried out by Lowry’s method [1], glycogen estimation by Kemp A. Vankits and Haljnimgem A.J.M., [2] and lipid estimation by Folch, J., Lees, M. and Sloane-Stanley, G. H., [3] method. Results, after comparison between cestode parasites i.e. Moniezia Sp. and host intestine (non-infected and infected intestine of host Capra hircus(L) indicates that the protein and lipid concentration is lower whereas the glycogen concentration is higher in Moniezia Sp. as compare to host intestine.

Human Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Response.

Human milk harbors complex carbohydrates, including human milk oligosaccharides (HMOs), the third most abundant component after lactose and lipids. HMOs have been shown to impact intestinal microbiota, modulate the intestinal immune response, and prevent pathogenic bacterial binding by serving as decoy receptors. However, the direct effect of HMOs on intestinal function and immunity remains to be elucidated. To address this knowledge gap, 21-day-old germ-free mice (C57BI/6) were orally gavaged with 15 mg/day of pooled HMOs for 7 or 14 days and euthanized at day 28 or 35. A set of mice was maintained until day 50 to determine the persistent effects of HMOs. Control groups were maintained in the isolators for 28, 35, or 50 days of age. At the respective endpoints, intestinal tissues were subjected to histomorphometric and transcriptomic analyses, while the spleen and mesenteric lymph nodes (MLNs) were subjected to flow cytometric analysis. The small intestine (SI) crypt was reduced after HMO treatment relative to control at days 28 and 35, while the SI villus height and large intestine (LI) gland depth were decreased in the HMO-treated mice relative to the control at day 35. We report significant HMO-induced and location-specific gene expression changes in host intestinal tissues. HMO treatment significantly upregulated genes involved in extracellular matrix, protein ubiquitination, nuclear transport, and mononuclear cell differentiation. CD4+ T cells were increased in both MLNs and the spleen, while CD8+ T cells were increased in the spleen at day 50 in the HMO group in comparison to controls. In MLNs, plasma cells were increased in HMO group at days 28 and 35, while in the spleen, only at day 28 relative to controls. Macrophages/monocytes and neutrophils were lower in the spleen of the HMO group at days 28, 35, and 50, while in MLNs, only neutrophils were lower at day 50 in the 14-day HMO group. In addition, diphtheria toxoid and tetanus toxoid antibody–secreting cells were higher in HMO-supplemented group compared to controls. Our data suggest that HMOs have a direct effect on gastrointestinal tract metabolism and the immune system even in the absence of host microbiota.

Food additive sodium bisulfite induces intracellular imbalance of biothiols levels in NCM460 colonic cells to trigger intestinal inflammation in mice

Sulfites and other preservatives are considered food additives to prevent pathogen growth in food, and they are generally regarded as safe since the late 1950s. However, the possible effects of sulfites on potential damage to host intestinal tissue remain largely unexplored. Given that endogenous sulfite mainly comes from the metabolism of biothiol, we attempted to clarify the relationship among biothiol levels, gut and food additives sulfite, including sodium bisulfite (NaHSO3), and the possible mechanism of sulfite affecting the intestine. In the present study, the NaHSO3 treatments markedly increased the homocysteine (Hcy) level but decreased the cysteine (Cys) level by promoting the expression of Hcy synthase and inhibiting the activities of cystathionine β-synthase and cystathionine γ-lyase in NCM460 cells. The level of methionine (Met) was not significantly changed, but NaHSO3 promoted ROS-mediated NF-κB signaling pathway, and increased the expressions of proinflammatory cytokines by regulating the levels of Hcy and Cys in NCM460 cells. Vitamin B6 (VB6) supplementation successfully ameliorated NaHSO3-induced damage in NCM460 cells and the colon of Balb/c mice. Altogether, our study provided valuable insights into the safety evaluation of food preservatives. Besides, VB6 could be used as a promising candidate in novel therapies for sodium bisulfite-induced intestinal inflammation.

Secretory acetylcholinesterase activities in fresh Ascaridia galli adult (Nematoda), excretory/secretory products, post-secretory parasite and gastrointestinal tissue of host Gallus gallus domesticus: A preliminary comparative study in host-parasite relationship

Acetylcholinesterase (AChE), an esterase enzyme, terminates synaptic transmission by hydrolyzing the neurotransmitter acetylcholine into acetate and choline. Found in membrane-bound form, AChE has also been reported to be secreted in soluble form by numerous enteric helminth parasites. Secretory AChE is considered to be an immunomodulator that may promote the survival of parasites against the host’s immune response. Our aim was to investigate the immunomodulation and survival strategy of helminth parasites Ascaridia galli inside the host Gallus gallus domesticus through analysis of AChE activity. The parasites, host intestinal tissue and post-secretory parasites were subjected to centrifugation, followed by AChE activity determination. The AChE activities among intestinal tissue, fresh parasites, excretory/secretory (E/S) product and post-secretory parasites were even compared. An inverse relationship between the reduced enzyme activity of the host’s intestinal tissue and the increased enzyme activity in the parasite was observed. Our study indicates that the increased AChE activities in fresh parasites, postsecretory parasites and E/S product are their survival strategy as well as a part of their adaptive features vis-à-vis the hostile environment of the host’sintestine.

Morphological and histopathological studies of Thelandros chalcidae (Oxyuroidea: Pharyngodonidae) infecting Chalcides ocellatus from Egypt

BackgroundThelandros (Pharyngodonidae) is a gastrointestinal nematode parasite with a life cycle including lizards as main hosts. Thelandros chalcidae collected from the large intestine of the Egyptian ocellated skink, Chalcides ocellatus were described and illustrated by light and scanning electron microscopes. Seven out of fifteen (46.66%) of the examined lizards were found to be naturally infected. Also, host intestinal tissues were evaluated from hematoxylin/eosin-stained sections to describe any histopathological changes.ResultsMicroscopic examinations revealed that the recovered pharyngodonid species characterized by mouth with triangular opening and surrounded by six simple lips, the cuticle had regular transverse annulations extending from the posterior margin of the lips to the end of the body. Male was cylindrical with distinct truncated posterior end and measured 1.59–1.86 (1.64 ± 0.10) long and 0.29–0.37 (0.32 ± 0.01) in maximum width at the level of mid-body. Female measured 1.72–2.43 (1.85 ± 0.2) long and 0.36–0.49 (0.42 ± 0.01) maximum width at the mid-body level, terminated posteriorly in a short, stout spike. Histological studies observed structural alterations represented by leukocytic infiltration, villi atrophy, and muscularis degeneration. These changes were indicative of inflammatory and degenerative reaction due to Thelandros chalcidae infection.ConclusionThe present morphological study revealed that the recovered pharyngodonid species was Thelandros chalcidae causing pathological alterations in Chalcides ocellatus intestinal tissues.

Vibrio cholerae toxin coregulated pilus provokes inflammatory responses in Coculture model of Caco-2 and peripheral blood mononuclear cells (PBMC) leading to increased colonization.

The aim of this study was to assess the modulatory effect of TcpA in the expression of CEACAM1 adhesin molecule and IL-1, IL-8, and TNF-α pro-inflammatory cytokines in the Coculture model of Caco-2/PBMC (peripheral blood mononuclear cell) that can mimic the intestinal milieu. The TcpA gene from Vibrio cholerae ATCC14035 was cloned in pET-28a and transformed into Escherichia coli Bl-21. The recombinant TcpA-His6 protein was expressed and purified using Ni-column chromatography. The sequencing of transformed plasmid and Western blot analysis of purified protein confirmed the identity of rTcp. The cytotoxicity of different concentrations of recombinant protein for human colon carcinoma cell line (human colorectal adenocarcinoma cell [Caco-2 cell]) was assessed by MTT assay and showed viability of 92%, 82%, and 70%, for 10 µg/mL of TcpA after 24, 48, and 72 h, respectively. Co-cultures of Caco-2 and PBMCs were used to mimic the intestinal milieu and treated with different concentrations of rTcpA (1, 5, 10, and 50 µg/mL). Our data showed about 2.04-, 3.37-, 3.68-, and 42.7-fold increase in CEACAM1 gene expression, respectively, compared with the nontreated Caco-2/PBMC Coculture. Moreover, the expression of IL-1, IL-8, and TNF-α genes was significantly increased up to 15.75-, 7.04-, and 80.95-folds, respectively. In conclusion, V. cholerae TcpA induces statistically significant dose-dependent stimulatory effect on TNF-α, IL-,1, and IL-8 pro-inflammatory cytokines expression. Of these, TNF-α was much more affected which, consequently, elevated the CEACAM1 expression level in IECs. This suggests that TcpA protein is a critical effector as an inducer of increased adhesion potential of V. cholera as well as inflammatory responses of host intestinal tissue.

CexE Is a Coat Protein and Virulence Factor of Diarrheagenic Pathogens.

CexE is a 12 kDa protein that was originally reported to be present in just three strains of enterotoxigenic Escherichia coli (ETEC); a frequent cause of diarrheal illnesses worldwide. However, an examination of sequenced genomes has revealed that CexE is actually present in a majority of ETEC strains. In addition, homologs of CexE are present in enteroaggregative E. coli (EAEC), Yersinia enterocolitica, Providencia alcalifaciens, and Citrobacter rodentium. Although it has been hypothesized that CexE and its homologs are virulence factors, this has yet to be tested. Thus the primary aim of this study was to determine if these proteins contribute to pathogenicity. Our secondary aim was determine if they are secreted coat proteins. Here we report that all neonatal mice infected with a wild-type strain of C. rodentium perished. In contrast a cexE mutant was significantly attenuated with 45% neonate survival. In adult mice the wild-type strain reached significantly higher loads in the large intestines and were shed in greater numbers than cexE mutants. Secretion of the CexE homolog in EAEC is dependent upon an atypical Type I secretion system that accepts its client from the periplasm rather than the cytoplasm. Insertion mutants of cexC, the putative ATPase of the CexE secretion system, were attenuated in our murine model. In vitro we found that CexC is required for the secretion of CexE to the outer membranes of both ETEC and C. rodentium. Secretion is not constitutive because CexE accumulates in the periplasm when the two pathogens are cultured under noninducing conditions. Although secretion conditions differ between ETEC and C. rodentium, secreted CexE remains predominantly associated with the outer membranes of both species. In aggregate these findings demonstrate that CexE is a secreted coat protein and virulence factor that promotes colonization of host intestinal tissues by enteric pathogens.

Commensal-derived metabolites govern Vibrio cholerae pathogenesis in host intestine

BackgroundRecent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels.ResultsHere, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice.ConclusionsOverall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.

Fasting Reduces Intestinal Radiotoxicity, Enabling Dose-Escalated Radiation Therapy for Pancreatic Cancer

Chemotherapy combined with radiation therapy is the most commonly used approach for treating locally advanced pancreatic cancer. The use of curative doses of radiation in this disease setting is constrained because of the close proximity of the head of the pancreas to the duodenum. The purpose of this study was to determine whether fasting protects the duodenum from high-dose radiation, thereby enabling dose escalation for efficient killing of pancreatic tumor cells. C57BL/6J mice were either fed or fasted for 24 hours and then exposed to total abdominal radiation at 11.5 Gy. Food intake, body weight, overall health, and survival were monitored. Small intestines were harvested at various time points after radiation, and villi length, crypt depth, and number of crypts per millimeter of intestine were determined. Immunohistochemistry was performed to assess apoptosis and double-strand DNA breaks, and microcolony assays were performed to determine intestinal stem cell regeneration capacity. A syngeneic KPC model of pancreatic cancer was used to determine the effects of fasting on the radiation responses of both pancreatic cancer and host intestinal tissues. We demonstrated that a 24-hour fast in mice improved intestinal stem cell regeneration, as revealed by microcolony assay, and improved host survival of lethal doses of total abdominal irradiation compared with fed controls. Fasting also improved survival of mice with orthotopic pancreatic tumors subjected to lethal abdominal radiation compared with controls with free access to food. Furthermore, fasting did not affect tumor cell killing by radiation therapy and enhanced γ-H2AX staining after radiation therapy, suggesting an additional mild radiosensitizing effect. These results establish proof of concept for fasting as a dose-escalation strategy, enabling ablative radiation in the treatment of unresectable pancreatic cancer.

Contribution of sulfate-reducing bacteria to homeostasis disruption during intestinal inflammation

Alteration in microbial populations and metabolism are key events associated with disruption of intestinal homeostasis and immune tolerance during intestinal inflammation. A substantial imbalance in bacterial populations in the intestine and their relationships with the host have been observed in patients with inflammatory bowel disease (IBD), believed to be part of an intricate mechanism of triggering and progression of intestinal inflammation. Because elevated numbers of sulfate-reducing bacteria (SRB) have been found in the intestines of patients with IBD, the study of their interaction with intestinal cells and their potential involvement in IBD has been the focus of investigation to better understand the intestinal pathology during IBD, as well as to find new ways to treat the disease. SRB not only directly interact with intestinal epithelial cells during intestinal inflammation but may also promote intestinal damage through generation of hydrogen sulfide at high levels. Herein we review the literature to discuss the various aspects of SRB interaction with host intestinal tissue, focusing on their interaction with intestinal epithelial and immune cells during intestinal inflammation.

Cavisoma magnum (Cavisomidae), a unique Pacific acanthocephalan redescribed from an unusual host, Mugil cephalus (Mugilidae), in the Arabian Gulf, with notes on histopathology and metal analysis.

Cavisoma magnum (Southwell, 1927) Van Cleave, 1931 was originally described from a sea bass, Serranus sp. and spotted surgeonfish, Ctenochaetus strigosus (Perciformes) off Sri Lanka before its more recent redescription from milkfish in the Philippines in 1995. These reports were based on only light infections of their host fishes. Of the few flathead grey mullets, Mugil cephalus (Mugilidae), that we examined in the Arabian Gulf, one fish was infected with 1,450 worms. One milkfish, Chanos chanos (Chanidae), from the same location in the Arabian Gulf, was also heavily infected with specimens of C. magnum. The descriptions of this unique large worm are revised and for the first time, we provide SEM images, new systematic observations, metal analysis of hooks showing extremely high levels of sulfur, and histopathology in the mullet intestinal tissue. Adjustments and corrections of previous descriptive accounts are made. The histopathology studies show extensive damage to the host intestinal tissue including epithelial necrosis, hemorrhaging and worm encapsulation. There is an extensive amount of host connective tissue surrounding the worm. Results of x-ray analysis displayed high levels of sulfur in proboscis hooks, especially at the tips and edges of these attachment structures.

Gnathostomatoidea Nematode: Parasite of &lt;i&gt;Sillago sihama&lt;/i&gt; Forsskal, 1775, Sillaginidae, and &lt;i&gt;Argyrops spinifer&lt;/i&gt; Forsskal, 1775, King soldier bream, in the Iraqi Marine Water Fishes, with Notes on Clinical Pathology and Feeding Habits of Infection

Background: The present finding describes third-stage larvae (L3) nematode (Gnathostomatidae) cysts parasitizing the intestinal serosa of the digestive tract of Sillago sihama (Forsskal, 1775) and Argyrops spinifer (Forsskal, 1775, King soldier bream) fishes collected from the Arabian Gulf. Objective: Two species of Gnathostomatidae are recorded, Gnathostoma sp and Gnathostoma binucleatum Almeyda-Artigas, 1991. The gross clinical pathology examination showed extensive damage to the host intestinal tissue, including epithelial necrosis, hemorrhaging, worm encapsulation, and the presence of live larvae encysted and adult in skeletal muscles of fishes causing lesions including mild hyperplasia of fibrous connective tissue around the parasite. The cross examination of fish intestines revealed food items containing parts of the animal body, appendages, Chela, and parts of the carapace of crustaceans. Most food items found in all months also including annelids (polychaetes) in high percentage in November Volume of food items were related to fish size. Juveniles appear to feed mainly on crustaceans and the adults mainly feed on crustaceans, molluscs, polychaetes, echinoderms, and teleosts, among other items. The summer was apparently not the season of parasite infection. The prevalence of infection with Gnathostoma binucleatum was low (6 of 57 fish), whereas the prevalence of infection with Gnathostoma sp. was 3 of 57 fish. These findings of Gnathostomatids represent new records of these parasites in Arabian Gulf fishes. More study needed to recognize on the larval stage parasite infection and their clinic pathology to provide a basic understanding of the general principles of the pathogenesis and pathology of Gnathostomiasis, and the relationship between fish length, food items and infection.

Mucosal Bioengineering: Gut in a Dish

Studying the interactions between commensal microbes and host intestinal tissue networks is challenging due to the complexity and inaccessibility of the system. A recent study reports a novel organ culture system that will enhance our ability to dissect these interactions.

Ikaros Inhibits Group 3 Innate Lymphoid Cell Development and Function by Suppressing the Aryl Hydrocarbon Receptor Pathway

Group 3 innate lymphoid cells (ILC3s) expressing the transcription factor (TF) RORγt are important for the defense and homeostasis of host intestinal tissues. The zinc finger TF Ikaros, encoded by Ikzf1, is essential for the development of RORγt(+) fetal lymphoid tissue inducer (LTi) cells and lymphoid organogenesis, but its role in postnatal ILC3s is unknown. Here, we show that small-intestinal ILC3s had lower Ikaros expression than ILC precursors and other ILC subsets. Ikaros inhibited ILC3s in a cell-intrinsic manner through zinc-finger-dependent inhibition of transcriptional activity of the aryl hydrocarbon receptor, a key regulator of ILC3 maintenance and function. Ablation of Ikzf1 in RORγt(+) ILC3s resulted in increased expansion and cytokine production of intestinal ILC3s and protection against infection and colitis. Therefore, in contrast to being required for LTi development, Ikaros inhibits postnatal ILC3 development and function to regulate gut immune responses at steady state and in disease.

Cardiolipins Act as a Selective Barrier to Toll-Like Receptor 4 Activation in the Intestine.

Intestinal homeostasis mechanisms must protect the host intestinal tissue from endogenous lipopolysaccharides (LPSs) produced by the intestinal microbiota. In this report, we demonstrate that murine intestinal fecal lipids effectively block Toll-like receptor 4 (TLR4) responses to naturally occurring Bacteroidetes sp. LPS. Cardiolipin (CL) represents a significant proportion of the total intestinal and fecal lipids and, furthermore, potently antagonizes TLR4 activation by reducing LPS binding at the lipopolysaccharide binding protein (LBP), CD14, and MD-2 steps of the TLR4 signaling pathway. It is further demonstrated that intestinal lipids and CL are less effective at neutralizing more potent Enterobacteriaceae-type LPS, which is enriched in feces obtained from mice with dextran sodium sulfate (DSS)-treated inflammatory bowel disease. The selective inhibition of naturally occurring LPS structures by intestinal lipids may represent a novel homeostasis mechanism that blocks LPS activation in response to symbiotic but not dysbiotic microbial communities. The guts of animals harbor a variety of Gram-negative bacteria associated with both states of intestinal health and states of disease. Environmental factors, such as dietary habits, can drive the microbial composition of the host animal's intestinal bacterial community toward a more pathogenic state. Both beneficial and harmful Gram-negative bacteria are capable of eliciting potentially damaging inflammatory responses from the host intestinal tissues via a lipopolysaccharide (LPS)-dependent pathway. Physical mucosal barriers and antibodies produced by the intestinal immune system protect against the undesired inflammatory effects of LPS, although it is unknown why some bacteria are more effective at overcoming the protective barriers than others. This report describes the discovery of a lipid-type protective barrier in the intestine that reduces the deleterious effects of LPSs from beneficial bacteria but is less effective in dampening the inflammatory effects of LPSs from harmful bacteria, providing a novel mechanistic insight into inflammatory intestinal disorders.