[Multiple myeloma with t (8;14) and t (11;14) and extramedullary infiltration of multiple organs].

A 69-year-old man presented with lumbago and was diagnosed with multiple myeloma (IgD-λ type, R-ISS stage II) with bone-destructive lesions in the lumbar spine and sacrum. Chromosome analysis showed t (8;14)(q24;q32) and t (11;14)(q13;q32). Treatment with daratumumab, lenalidomide, and dexamethasone resulted in partial response, but the disease relapsed, with a copy number increase in t (11;14) and abnormal amplification of the 1q21 region. The patient was treated for CMV enteritis, and was admitted to the hospital due to sudden abdominal pain. Gastrointestinal perforation was diagnosed by CT scan showing free air and wall thickening in the small intestine. Emergency surgery was performed, and the tumors in the perforated area were positive for CCND1 but negative for MYC on immunostaining. The patient's general condition did not improve after the surgery and he died. Pathological autopsy revealed extramedullary infiltration of multiple organs in addition to the small intestine. Extramedullary infiltration is thought to be caused by clonal evolution, and further research is warranted to clarify its pathogenesis and establish effective therapeutic strategies in high-risk patients.

Maternal consumption of fish oil protected breast-fed piglets against Escherichia coli lipopolysaccharide-induced damage through reshaping of intestinal fatty acids profile.

It has been well documented that n-3 polyunsaturated fatty acids (n-3 PUFA) can alleviate inflammation caused by Escherichia coli (E. coli) lipopolysaccharides (LPS), the etiologic agents that causing yellow or white dysentery in young pigs. However, it remains unclear whether the increase in n-3 PUFA availability could enhance the ability of nursery pigs to resist invasion by E. coli. LPS. Twenty-four 21-day-old female piglets, each two of them from the same sow fed the beef tallow (BT) or fish oil (FO) diets, were allocated into four treatment groups: BT-CON, piglets from the BT-fed sows and intraperitoneally injected with saline (9 g/L); BT-LPS, piglets from the BT-fed sows and injected with LPS (100 µg/kg body weight); FO-CON, piglets from the FO-fed sows and injected with saline; FO-LPS, piglets from the FO-fed sows and injected with LPS. Following 2 h of LPS challenge, the magnitudes of increase in body temperature approached to a marked (p < 0.01) difference between the BT-CON and BT-LPS piglets, whereas the dramatic (p < 0.01) difference between the FO-CON and FO-LPS piglets was only observed at 4 h post LPS challenge. The body temperature averaged across the time points evaluated was about 0.2°C lower (p < 0.05) in the FO group than in the BT group. The FO group had lower (p < 0.05) mean corpuscular hemoglobin concentration, lower increase in serum interleukin (IL)-1ß (p < 0.10) and IL-8 (p < 0.05) levels, higher (p < 0.01) serum albumin concentration, and higher (p = 0.10) ratios of jejunum villus height to crypt depth than the BT group. The FO group had much higher (p < 0.0001) ileal content of C20:5n3, C24:0, and C22:6n3, which were 2-4 times the content of the BT group. LPS challenge resulted in decreased (p < 0.05) intestinal C20:1 and C20:5n3 content, and the decrease (p < 0.05) in intestinal C20:3n6 and C24:1 content was observed in the BT-LPS piglets rather than in the FO-LPS piglets. Taken together, this study indicated that maternal consumption of fish oil protected breast-fed piglets against E. coli LPS-induced damage through reshaping of intestinal fatty acids profile, which sheds new light on the development of nutritional strategies to enhance the ability of young pigs to resist E. coli invasion.

Ultra-high-frequency ultrasound (48-70 MHz) is a promising tool for improved gastrointestinal diagnostics in infants.

AIM: To investigate the clinical feasibility of ultra-high-frequency abdominal ultrasound (UHFUS) scans of preterm and term infants. METHODS: Prospectively, 19 healthy term newborn infants were examined with conventional ultrasound (CUS) (Toshiba, Aplio i700, linear probe 14L5) and UHFUS (Visualsonics VevoMD, linear probes UHF48 and UHF70) according to a standardised protocol. Measurements of wall thickness were performed for; stomach, small intestine, colon and peritoneum. Five preterm infants, with or without suspected necrotising enterocolitis (NEC), were also examined with UHF48. Of these, only one was later diagnosed with NEC. RESULTS: Differences between CUS and UHFUS (UHF48) were found in measurements of thickness; for peritoneum 0.25 versus 0.13 mm (p < 0.001), small intestine 0.76 versus 0.64 mm (p = 0.039) and colon 0.7 versus 0.47 mm (p < 0.001) in healthy term infants. Gaining frequency from 46 to 71 MHz showed a mean reduction in measurements of peritoneum from 0.13 to 0.09 mm (p < 0.001). One preterm infant with NEC showed a fivefold and twofold increase in peritoneal and gastrointestinal wall thickness respectively, compared to healthy preterm infants. CONCLUSION: UHFUS was a clinically feasible, promising method with potential to improve gastrointestinal diagnostics in infants. Lower peritoneum thickness and gastrointestinal wall thickness were demonstrated with UHFUS compared to CUS, suggesting an overestimation by CUS.

Protective effects of Lactococcus lactis subsp. lactis HFY14 supplementation on the brain, intestines, and motor function of antibiotic-treated mice.

Introduction: This study aimed to explore the anti-oxidative and anti-inflammatory properties of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) and investigate its effects on the intestinal barrier, cranial nerve, and motor function in mice treated with antibiotics. Methods: Mice were administered an antibiotic mixture (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole file 5 mg/mL, and lipopolysaccharide 1.5 µg/mL) intraperitoneally, and oxidative stress and inflammatory markers in the serum and brain tissues, and liver index were measured. H&E staining was performed to detect pathological alterations in brain tissues. The expression of intestinal-barrier-related genes and that of genes involved in inflammatory pathways in the brain were detected using polymerase chain reaction (PCR). Results: LLSLHFY14 administration extended the weight-loaded swimming and running times of mice and decreased the liver index. Moreover, the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the serum and brain tissue were reduced, whereas those of superoxide dismutase (SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated. Elevated brain expression of the protein kinase B (AKT)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase 1 (ERK1) pathway, decreased brain expression of the IL-6 gene, and elevated cecum expression of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes were noted. LLSLHFY14 supplementation significantly increased Bacteroidetes expression but decreased Firmicutes expression, thus increasing the Bacteroidetes/Firmicutes ratio. Discussion: Overall, LLSLHFY14 supplementation ameliorated antibiotic-induced oxidative stress and inflammation in the mouse central nervous system, intestinal barrier dysfunction, and increased motor function, thus confirming its potential application as probiotics.

Complications unveiled: A detailed case report on mesh migration post-incisional hernia repair.

INTRODUCTION AND IMPORTANCE: Repairing incisional abdominal wall hernia with nonabsorbable meshes is one of the most common procedures in general surgery. Mesh migration into the intestine is rare but a serious complication. It can occur months or even years after surgery and often presents with vague abdominal pain, making diagnosis tricky. CASE PRESENTATION: We report a rare case of a 52-year-old female presenting a small bowel obstruction secondary to mesh migration from the abdominal wall into the intestine, 10 years after repeated surgical repair of a ventral incisional hernia. At surgery, a mesh was migrated into a small bowl. The patient had a small bowel resection. The postoperative course was simple and the patient was discharged after 5 days. CASE DISCUSSION: Incisional hernia repair with mesh is one of the most commonly performed surgical procedures worldwide. Many complications have been linked to the use of mesh; among the most frequently reported are seromas, hematomas, and infections. Mesh migration remains an uncommon event after incisional hernia repair, and even rarer when considering complete migration within the intestinal lumen. The exact cause of this complication remains unknown. Multiple hypotheses have been proposed for mesh migration. Abdominal pain, intermittent or persistent intestinal obstruction, mass formation, and viscus perforation represent the most common clinical manifestation. Total removal of the mesh via laparoscopy or laparotomy is recommended, along with either partial or entire resection of the organ. CONCLUSION: Mesh migration is a an uncommon possible complication in case of incisional hernia mesh repair and it requires often surgical intervention.

Primary mantle-cell lymphoma of small intestine presenting with intussusceptions: A case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Mantle cell lymphoma is a rare type of non-Hodgkin's lymphoma which accounts for 5 % of all cases. Patients present with an advanced form of the disease. We present here a case of ileocolic intussusception secondary to mantle cell lymphoma which was revealed by abdominal pain and vomiting that was treated by surgical resection followed by chemotherapy. CASE PRESENTATION: This report illustrates the case of a 34-year-old male who presented with abdominal pain and vomiting. Imageology demonstrated an ileocolic intussusception which was treated with hemicolectomy followed by chemotherapy. Histopathology confirmed the diagnosis of Mantle cell lymphoma. CLINICAL DISCUSSION: Mantel cell lymphoma is a rare type of B-cell cancer. Patients are generally diagnosed with an advanced stage of the disease. Ileocolic intussusception is an uncommon presentation. Surgery is the pillar of the treatment. Resection depends on the extent and location of the lesion. Postoperative chemotherapy is crucial and it increases survival rate. CONCLUSION: Mantle cell lymphoma is a rare subgroup of B-cell lymphomas. Ileocolic intussusception is a complicated form of the disease. Surgery combined with chemotherapy is the mainstay of the treatment. Diagnosis is confirmed by histological analysis of the surgical specimen.

Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome.

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface. Continued disruption of the intestinal mucus barrier through such a mechanism may play a role in the perpetuation of the intestinal inflammatory process.

Moniezia benedeni drives the SNAP-25 expression of the enteric nerves in sheep's small intestine.

BACKGROUND: The neuroimmune network plays a crucial role in regulating mucosal immune homeostasis within the digestive tract. Synaptosome-associated protein 25 (SNAP-25) is a presynaptic membrane-binding protein that activates ILC2s, initiating the host's anti-parasitic immune response. METHODS: To investigate the effect of Moniezia benedeni (M. benedeni) infection on the distribution of SNAP-25 in the sheep's small intestine, the recombinant plasmid pET-28a-SNAP-25 was constructed and expressed in BL21, yielding the recombinant protein. Then, the rabbit anti-sheep SNAP-25 polyclonal antibody was prepared and immunofluorescence staining was performed with it. The expression levels of SNAP-25 in the intestines of normal and M. benedeni-infected sheep were detected by ELISA. RESULTS: The results showed that the SNAP-25 recombinant protein was 29.3 KDa, the titer of the prepared immune serum reached 1:128,000. It was demonstrated that the rabbit anti-sheep SNAP-25 polyclonal antibody could bind to the natural protein of sheep SNAP-25 specifically. The expression levels of SNAP-25 in the sheep's small intestine revealed its primary presence in the muscular layer and lamina propria, particularly around nerve fibers surrounding the intestinal glands. Average expression levels in the duodenum, jejunum, and ileum were 130.32 pg/mg, 185.71 pg/mg, and 172.68 pg/mg, respectively. Under conditions of M. benedeni infection, the spatial distribution of SNAP-25-expressing nerve fibers remained consistent, but its expression level in each intestine segment was increased significantly (P < 0.05), up to 262.02 pg/mg, 276.84 pg/mg, and 326.65 pg/mg in the duodenum, jejunum, and ileum, and it was increased by 101.06%, 49.07%, and 89.16% respectively. CONCLUSIONS: These findings suggest that M. benedeni could induce the SNAP-25 expression levels in sheep's intestinal nerves significantly. The results lay a foundation for further exploration of the molecular mechanism by which the gastrointestinal nerve-mucosal immune network perceives parasites in sheep.

Improved Preservation of Rat Small Intestine Transplantation Graft by Introduction of Mesenchymal Stem Cell-Secreted Fractions.

Segmental grafts from living donors have advantages over grafts from deceased donors when used for small intestine transplantation. However, storage time for small intestine grafts can be extremely short and optimal graft preservation conditions for short-term storage remain undetermined. Secreted factors from mesenchymal stem cells (MSCs) that allow direct activation of preserved small intestine grafts. Freshly excised Luc-Tg LEW rat tissues were incubated in preservation solutions containing MSC-conditioned medium (MSC-CM). Preserved Luc-Tg rat-derived grafts were then transplanted to wild-type recipients, after which survival, injury score, and tight junction protein expression were examined. Luminance for each graft was determined using in vivo imaging. The findings indicated that 30-100 and 3-10 kDa fractions of MSC-CM have superior activating effects for small intestine preservation. Expression of the tight-junction proteins claudin-3, and zonula occludens-1 preserved for 24 h in University of Wisconsin (UW) solution containing MSC-CM with 50-100 kDa, as shown by immunostaining, also indicated effectiveness. Reflecting the improved graft preservation, MSC-CM preloading of grafts increased survival rate from 0% to 87%. This is the first report of successful transplantation of small intestine grafts preserved for more than 24 h using a rodent model to evaluate graft preservation conditions that mimic clinical conditions.

Review article: Management of the child with refractory constipation.

BACKGROUND: Caring for children with constipation refractory to conventional treatment can be challenging and management practices vary widely. AIMS: To review recent advances in the evaluation and treatment of children with refractory constipation and to propose an algorithm that incorporates the latest evidence and our institutional experience. METHODS: We performed a literature review on diagnostic tests and treatment options for children with refractory constipation. RESULTS: Evaluation of a child with refractory constipation seeks to better understand factors contributing to an individual child's presentation. Anorectal manometry evaluating for a rectal evacuation disorder and colonic manometry evaluating for colonic dysmotility can guide subsequent treatment. For the child who has not responded to conventional treatment, a trial of newer medications like linaclotide can be helpful. Transanal irrigation offers a safe and effective alternative for families able to administer daily rectal treatment. Despite mixed evidence in children, pelvic floor biofeedback therapy can help some children with pelvic floor dyssynergia. For younger children unable to cooperate with pelvic floor therapy, or older children with refractory symptoms, internal anal sphincter botulinum toxin injection can be beneficial. Antegrade continence enema treatment can be effective for children with either normal colonic motility or segmental dysmotility. Sacral nerve stimulation is generally reserved for symptoms that persist despite antegrade continence enemas, particularly if faecal incontinence is prominent. In more severe cases, temporary or permanent colonic diversion and segmental colonic resection may be needed. CONCLUSIONS: Recent advances offer hope for children with refractory constipation.

Detecting emergence of ruptures in individual layers of the stretched intestinal wall using optical coherence elastography: A pilot study.

We report a new application of compression optical coherence elastography (C-OCE) to monitor the emergence of ruptures in individual layers of longitudinally stretched small-intestine walls using tissue samples (n = 36) from nine minipigs. Before stretching, C-OCE successfully estimated stiffness for each intestine-wall layer: longitudinal muscular layer with serosa, circumferential muscular layer, submucosa and mucosa. In stretched samples, C-OCE clearly visualized initial stiffening in both muscular layers. By 25% elongation, a sharp stiffness decrease for the longitudinal muscular layer, indicated emergence of tears in all samples. With further stretching, for most samples, ruptures emerged in the circumferential muscular layer and submucosa, while mucosa remained undamaged. Histology confirmed the OCE-revealed damaging and absence of tissue damage for ~15% elongation. Thus, C-OCE has demonstrated a high potential for determining the safety tissue-stretching threshold which afterward may be used intraoperatively to prevent rupture risk in intestinal tissues stretched during various diagnostic/therapeutic procedures.

Localization and function of humanized F508del-CFTR in mouse intestine following activation of Serum Glucocorticoid kinase 1 and Trikafta.

The CFTR modulator Trikafta has markedly improved lung disease for Cystic Fibrosis (CF) patients carrying the common delta F508 (F508del-CFTR) CFTR mutation. F508del-CFTR results in an apical trafficking defect and loss of function in CFTR-expressing epithelial cells. However, Trikafta has not resulted in improved gastrointestinal function in CF patients. A humanized mouse model of F508del-CFTR was recently generated to evaluate CFTR modulators and other compounds to treat human F508del-CFTR CF intestinal disease. Short-term (4h) treatment of rats with Dexamethasone (Dex) potently activates serum glucocorticoid kinase 1 (SGK1) and increases CFTR apical traffic and ion transport in the native intestine. This study examined CFTR localization and ion transport in intestinal segments from humanized F508del-CFTR mice following treatment with Dex in the presence/absence of Trikafta. Dex treatment improved apical CFTR localization and function but was inconsistent along intestinal segments. Combined treatment with Dex and Trikafta was superior to Dex alone but inconsistently improved CFTR localization and function. These data suggest further optimization of humanized CF mouse models will be necessary to test the efficacy of compounds to treat human CF intestinal disease.

Heterogenous Gene Expression of Bicellular and Tricellular Tight Junction-Sealing Components in the Human Intestinal Tract.

A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from the outer environment. The intercellular spaces between adjacent epithelial cells are sealed by bicellular and tricellular tight junctions (TJs). Although one strategy for enhancing intestinal drug absorption is to modulate these TJs, comprehensive gene (mRNA) expression analysis of the TJs components has never been fully carried out in humans. In this study, we used human biopsy samples of normal-appearing mucosa showing no endoscopically visible inflammation collected from the duodenum, jejunum, ileum, colon, and rectum to examine the mRNA expression profiles of TJ components, including occludin and tricellulin and members of the claudin family, zonula occludens family, junctional adhesion molecule (JAM) family, and angulin family. Levels of claudin-3, -4, -7, -8, and -23 expression became more elevated in each segment along the intestinal tract from the upper segments to the lower segments, as did levels of angulin-1 and -2 expression. In contrast, expression of claudin-2 and -15 was decreased in the large intestine compared to the small intestine. Levels of occludin, tricellulin, and JAM-B and -C expression were unchanged throughout the intestine. Considering their segment specificity, claudin-8, claudin-15, and angulin-2 appear to be targets for the development of permeation enhancers in the rectum, small intestine, and large intestine, respectively. These data on heterogenous expression profiles of intestinal TJ components will be useful for the development of safe and efficient intestinal permeation enhancers.

Adaptations in Gastrointestinal Nutrient Absorption and its Determinants During Pregnancy in Monogastric Mammals: A Scoping Review.

CONTEXT: Pregnancy increases nutrient demand, but how nutrient uptake and its determinants adapt to facilitate this is unclear. OBJECTIVE: This review aimed to identify and characterize evidence and evidence gaps regarding changes in gastrointestinal nutrient absorption and its determinants during pregnancy in monogastric mammals. DATA SOURCES: A scoping review of peer-reviewed sources was conducted across PubMed, Scopus, Web of Science, Embase, and ProQuest (theses and dissertations) databases. DATA EXTRACTION: Data extracted included species, pregnancy stages and outcomes. Where sufficient data for a given outcome was available, relative values were summarized graphically or in tables, to allow comparison across pregnancy stages and/or small intestine regions. Searches identified 26 855 sources, of which only 159 were eligible. Mechanistic studies were largely restricted to rodents, and most compared non- and late-pregnant groups, with fewer studies including early- or mid-pregnant groups. DATA ANALYSIS: During pregnancy, there is some evidence for greater capacity for glucose uptake but unchanged amino acid uptake, and good evidence for increased uptake of calcium, iron, and zinc, and slower gastrointestinal passage of nutrients. The available evidence indicates that acute glucose uptake, gastric emptying, and the activities of sucrase, maltase, and lactase do not change during pregnancy. Gaps in the knowledge include the effects of pregnancy on uptake of specific amino acids, lipids, and most minerals and vitamins. CONCLUSION: The results indicate that the gastrointestinal tract adapts during pregnancy to facilitate increased nutrient absorption. Additional data is required in order to assess the underlying mechanisms for and impacts on the absorption of many nutrients, as well as to determine the timing of these adaptations.

Acute and Long COVID Intestinal Changes in an Experimental Model of Coronavirus in Mice.

The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.

Slit2-Robo4 signal pathway and tight junction in intestine mediate LPS-induced inflammation in mice.

BACKGROUND: Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated. METHODS: The animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays. RESULTS: The C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1ß, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1ß and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. CONCLUSIONS: In this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.

Neuroimmune Interactions in the Intestine.

Recent advances have contributed to a mechanistic understanding of neuroimmune interactions in the intestine and revealed an essential role of this cross talk for gut homeostasis and modulation of inflammatory and infectious intestinal diseases. In this review, we describe the innervation of the intestine by intrinsic and extrinsic neurons and then focus on the bidirectional communication between neurons and immune cells. First, we highlight the contribution of neuronal subtypes to the development of colitis and discuss the different immune and epithelial cell types that are regulated by neurons via the release of neuropeptides and neurotransmitters. Next, we review the role of intestinal inflammation in the development of visceral hypersensitivity and summarize how inflammatory mediators induce peripheral and central sensitization of gut-innervating sensory neurons. Finally, we outline the importance of immune cells and gut microbiota for the survival and function of different neuronal populations at homeostasis and during bacterial and helminth infection.

Bacillus subtilis fmbj ameliorates lipopolysaccharide-induced intestinal dysfunction in broilers by enhancing the SIRT1/PGC1α pathway.

This study aimed to explore the impact of dietary Bacillus subtilis fmbj (BS) supplementation on acute intestinal dysfunction induced by lipopolysaccharide (LPS) in broilers. One hundred and eighty 1-day-old male Arbor Acres broilers were randomly divided into three treatment groups, each comprising ten replicates of 6 birds. On d 20, LPS-challenged (LPS group and LPS-BS group) and LPS-unchallenged (CON group) broilers received intraperitoneal injections of 1 mg/kg body weight LPS solution and an equivalent volume of sterile saline, respectively. Compared to the CON group, LPS disrupted (P < 0.05) the morphology of the small intestine (jejunum or ileum), exacerbated (P < 0.05) serum, small intestinal, and small intestinal mitochondrial antioxidant capacity, induced (P < 0.05) small intestinal oxidative damage, and altered (P < 0.05) the expression of genes and proteins related to antioxidants, cell adhesion, and mitochondrial function in the jejunum. The LPS-BS group exhibited a tendency towards improvement in small intestinal morphology, serum, small intestinal, and small intestinal mitochondrial antioxidant capacity, small intestinal oxidative damage, and the expression of genes and proteins related to antioxidants, cell adhesion, and mitochondrial function in the jejunum when compared to the LPS group. In conclusion, BS supplementation may confer protection against LPS-induced acute intestinal dysfunction in broilers by enhancing the activation of SIRT1/PGC1α, suggesting its potential as a valuable additive for the poultry industry.

Colon-derived Caco-2 cells support replication of hepatitis E virus genotype 1 strain Sar55 generated by reverse genetics.

The hepatitis E virus (HEV) is infecting over 20 million people annually with a high morbidity especially in pregnant women and immune-suppressed individuals. While HEV genotype 1 (HEV-1) infects only humans, genotype 3 (HEV-3) is zoonotic and commonly transmitted from infected animals to humans. Whereas a few reverse genetics systems enabling targeted genome manipulations exist for HEV-3, those for HEV-1 are still very limited, mainly because of inefficient cell culture replication. Here, the generation of HEV-1 strain Sar55 and HEV-3 strain 47832mc by transfecting in vitro-transcribed and capped virus genomes into different cell lines was attempted. Culture supernatants of colon-derived colorectal adenocarcinoma cell line Caco-2 contained HEV-1 and HEV-3 capable of infecting Caco-2 cells. Density gradient centrifugation analyses of culture supernatants confirmed that HEV-1 particles were quasi-enveloped in analogy to HEV-3 and that non-virion-associated capsid protein was secreted from cells. Following transfection or infection of Caco-2 cells, HEV-1 consistently reached higher titers than HEV-3 in culture supernatants, but HEV-1 generated by transfection of Caco-2 cells was unable to efficiently infect hepatoma cell lines PLC/PRF/5 or HuH7-Lunet BLR. Taken together, our results indicate that HEV-1 is able to exert a complete replication cycle in Caco-2 cells. An efficient cell culture system for this genotype will be useful for studying species tropism, but further research is required to determine the significance of HEV-1 replication in colon-derived cells.

Cannabidiol decreases histological intestinal injury in a neonatal experimental model of necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a severe inflammatory bowel disease in neonates. Our group has developed an experimental model of NEC, with an effectiveness of 73%. Cannabidiol (CBD) is an innovative treatment for neonatal cerebral hypoxic-ischemic pathologies due to its neuroprotective effect, as a potent anti-inflammatory and reducing oxidative stress substance. Our aim was to evaluate the effect of CBD on intestinal lesions in an experimental model of NEC. RESULTS: Mortality and intestinal histological damage was significantly lower in the CBD group compared to the rest (p<0.05), establishing CBD as a protective factor against the development of NEC (OR=0.0255; 95% CI=0.0015-0.4460). At IHQ level (TUNEL technique), a lower cell death rate was also observed in the CBD group compared to the VEH group (p<0.05). CONCLUSIONS: In our experimental model, intraperitoneal CBD acts as a protective factor against NEC, resulting in less histological damage and a lower rate of intestinal cell death.