Risk factors of recurrence after incisional hernia preperitoneal repair: a long-term retrospective single-center cohort study.

PURPOSE: To explore the risk factors for incisional hernia (IH) recurrence following open prepertioneal repair. METHODS: Patients diagnosed with primary IH who underwent open preperitoneal repair at our hospital were enrolled. Patients were assessed, and perioperative factors were collected. Recurrence surveys were performed at regular intervals throughout the long-term postoperative follow-up. The risk factors for IH recurrence were identified using univariate and multivariate analyses. RESULTS: This study included 145 patients. Significant differences were found between recurrence and non-recurrence patients regarding pulmonary ventilation function (PVT), age, body mass index (BMI), mesh materials, type of surgery (clean, clean-contaminated, or contaminated), surgical site infections (SSIs), maximum width of the hernia defect (MWHD), and site of incisional hernia (P < 0.01). The univariate survival analysis revealed that PVT abnormalities, age > 70 years, BMI > 27 kg/m2, porcine small intestine submucosal (PSIS) mesh, non-clean surgery, SSIs, MWHD > 10 cm, and location in the lateral zones were significant factors for IH recurrence after open preperitoneal repair. The multivariate survival analysis showed that PVT abnormalities, age > 70 years, BMI > 27 kg/m2, and PSIS mesh were independent risk factors for IH recurrence after open preperitoneal repair. CONCLUSIONS: We identified PVT abnormalities, age > 70 years, BMI > 27 kg/m2, and PSIS mesh as novel risk factors for IH recurrence after open preperitoneal repair.

Small intestine metastasis from endometrial carcinoma initially presented as enterocutaneous fistula: a case report and literature review.

Although endometrial cancer is the fourth most common malignancy among women, it rarely metastasizes to the small intestine. Cases of endometrial recurrence to the intestine clinically present with secondary anemia, melena, abdominal cramps, and epigastric pain. Only a dozen cases are reported in the literature, but none presented with an enterocutaneous fistula. In this report, we present a case of an 88-year-old female patient previously treated for endometrial adenocarcinoma with surgery and adjuvant radiotherapy. Fourteen months after the surgery, the patient presented with an enterocutaneous fistula on the anterior abdominal wall, which was confirmed to be a metastasis from the primary tumor. To our knowledge, this is the first case of endometrial cancer metastasizing to the small intestine with involvement of the anterior abdominal wall and the occurrence of an enterocutaneous fistula, which was treated with radical surgery.

Mucosal vaccination in a murine gnotobiotic model of Giardia lamblia infection.

Giardia lamblia is an important protozoan cause of diarrheal disease worldwide, delayed development and cognitive impairment in children in low- and middle-income countries, and protracted post-infectious syndromes in developed regions. G. lamblia resides in the lumen and at the epithelial surface of the proximal small intestine but is not mucosa invasive. The protozoan parasite is genetically diverse with significant genome differences across strains and assemblages. Animal models, particularly murine models, have been instrumental in defining mechanisms of host defense against G. lamblia, but mice cannot be readily infected with most human pathogenic strains. Antibiotic pretreatment can increase susceptibility, suggesting that the normal microbiota plays a role in controlling G. lamblia infection in mice, but the broader implications on susceptibility to diverse strains are not known. Here, we have used gnotobiotic mice to demonstrate that robust intestinal infection can be achieved for a broad set of human-pathogenic strains of the genetic assemblages A and B. Furthermore, gnotobiotic mice were able to eradicate infection with a similar kinetics to conventional mice after trophozoite challenge. Germ-free mice could also be effectively immunized by the mucosal route with a protective antigen, α1-giardin, in a manner dependent on CD4 T cells. These results indicate that the gnotobiotic mouse model is powerful for investigating acquired host defenses in giardiasis, as the mice are broadly susceptible to diverse G. lamblia strains yet display no apparent defects in mucosal immunity needed for controlling and eradicating this lumen-dwelling pathogen.

Preservation of conjugated primary bile acids by oxygenation of the small intestinal microbiota in vitro.

Bile acids play a critical role in the emulsification of dietary lipids, a critical step in the primary function of the small intestine, which is the digestion and absorption of food. Primary bile acids delivered into the small intestine are conjugated to enhance functionality, in part, by increasing aqueous solubility and preventing passive diffusion of bile acids out of the gut lumen. Bile acid function can be disrupted by the gut microbiota via the deconjugation of primary bile acids by bile salt hydrolases (BSHs), leading to their conversion into secondary bile acids through the expression of bacterial bile acid-inducible genes, a process often observed in malabsorption due to small intestinal bacterial overgrowth. By modeling the small intestinal microbiota in vitro using human small intestinal ileostomy effluent as the inocula, we show here that the infusion of physiologically relevant levels of oxygen, normally found in the proximal small intestine, reduced deconjugation of primary bile acids, in part, through the expansion of bacterial taxa known to have a low abundance of BSHs. Further recapitulating the small intestinal bile acid composition of the small intestine, limited conversion of primary into secondary bile acids was observed. Remarkably, these effects were preserved among four separate communities, each inoculated with a different small intestinal microbiota, despite a high degree of taxonomic variability under both anoxic and aerobic conditions. In total, these results provide evidence for a previously unrecognized role that the oxygenated environment of the small intestine plays in the maintenance of normal digestive physiology. IMPORTANCE: Conjugated primary bile acids are produced by the liver and exist at high concentrations in the proximal small intestine, where they are critical for proper digestion. Deconjugation of these bile acids with subsequent transformation via dehydroxylation into secondary bile acids is regulated by the colonic gut microbiota and reduces their digestive function. Using an in vitro platform modeling the small intestinal microbiota, we analyzed the ability of this community to transform primary bile acids and studied the effect of physiological levels of oxygen normally found in the proximal small intestine (5%) on this metabolic process. We found that oxygenation of the small intestinal microbiota inhibited the deconjugation of primary bile acids in vitro. These findings suggest that luminal oxygen levels normally found in the small intestine may maintain the optimal role of bile acids in the digestive process by regulating bile acid conversion by the gut microbiota.

Gluten-free foods are expensive and nutritionally imbalanced than their gluten-containing counterparts.

OBJECTIVES: Nutritional quality of gluten-free (GF) food products is very important, as patients with celiac disease consume these products for lifelong. There is paucity of data on the nutritional content and cost of GF food products compared with their gluten-containing (GC) counterparts from India (Asia). DESIGN: After a detailed market survey, packaged and labeled GF food products (n=485) and their packaged GC counterparts (n=790) from the supermarkets of Delhi (India) and e-commerce websites were included. Nutritional content and cost/100 g food (in US dollars) were calculated using the information on food label. RESULTS: Gluten-free food products were 232% (range: 118% to 376%) more expensive than their GC counterparts. Energy content of all GF food products was similar to their GC counterparts, except cereal-based snacks (GF: 445 kcal vs. GC: 510 kcal, p<0.001). The protein content was significantly lower in GF pasta and macaroni products (single-grain: GF: 6.5 g vs. GC:11. 5 g, p-0.002; multigrain: GF:7.6 g vs. GC:11.5 g, p-0.027), cereal flours (single-grain: GF: 7.6 g vs. GC: 12.3 g, p<0.001; multigrain: GF:10.9 g vs. GC: 14.1 g, p-0.009) and nutritional bars (GF: 21.81 g vs. GC:26 g, p-0.028) than their GC counterparts. Similarly, the dietary-fiber content of GF pasta and macaroni products, cereal flours, cereal premix and nutritional bars of GF foods was significantly lower than their GC counterparts. Gluten-free bread and confectionary items, biscuits and cookies and snacks had higher total fats and trans-fat content than their GC counterparts. Gluten-free cereal-based snacks had higher sodium content than their GC counterparts (GF: 820 mg vs. GC:670 mg; p<0.001). CONCLUSION: GF foods are significantly more expensive, contain less protein and dietary fiber and higher fat, trans-fat and sodium than their GC counterparts. Strategies must be developed to reduce the cost and improve the nutritional profile of GF foods.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic.

Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

A rare case of schwannoma of the small intestine discovered during intussusception.

A woman in her 60s with anemia was diagnosed with a small intestinal intussusception on computed tomography. She underwent a double-balloon endoscopy, which revealed submucosal tumor in the ileum. Suspected to be the cause of anemia and intussusception, surgical intervention was carried out, revealing it to be a schwannoma. Schwannomas of the small intestine are very rare, and because exophytic growths are common, intussusception due to luminal side development is even rarer.

Rare recurrence pattern after complete response to chemotherapy in a patient with rectal cancer: a case report.

BACKGROUND: Colorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare metastasis of anal cancer in the left bladder wall, followed by metastases to the small intestine and skin, after abdominoperineal resection and left lateral lymph node dissection with chemotherapy in a patient with clinician Stage IVa disease. CASE PRESENTATION: A 66-year-old man presented with 1-month history of bloody stool and anal pain and diagnosed with clinical Stage IVa anal cancer with lymph node and liver metastases (cT3, N3 [#263L], M1a [H1]). Systemic chemotherapy led to clinical complete response (CR) for the liver metastasis and clinical near-CR for the primary tumor. Robot-assisted laparoscopic perineal rectal resection and left-sided lymph node dissection were performed. Computed tomography during 18-month postoperative follow-up identified a mass in the left bladder wall, which was biopsied with transurethral resection, was confirmed as recurrent anal cancer by histopathologic evaluation. After two cycles of systemic chemotherapy, partial resection of the small intestine was performed due to bowel obstruction not responding to conservative therapy. The histopathologic evaluation revealed lymphogenous invasion of the muscularis mucosa and subserosa of all sections. Ten months after the first surgery for bowel obstruction and two months before another surgery for obstruction of the small intestine, skin nodules extending from the lower abdomen to the thighs were observed. The histopathologic evaluation of the skin biopsy specimen collected at the time of surgery for small bowel obstructions led to the diagnosis of skin metastasis of anal cancer. Although panitumumab was administered after surgery, the patient died seven months after the diagnosis of skin metastasis. CONCLUSIONS: This case illustrates the rare presentation of clinical Stage IVa anal cancer metastasizing to the bladder wall, small intestine, and skin several years after CR to chemotherapy.

Oral bioavailability of a noncoding RNA drug, TY1, that acts on macrophages.

All approved RNA therapeutics require parenteral delivery. Here we demonstrate an orally bioavailable formulation wherein synthetic noncoding (nc) RNA, packaged into lipid nanoparticles, is loaded into casein-chitosan (C2) micelles. We used the C2 formulation to deliver TY1, a 24-nucleotide synthetic ncRNA which targets the DNA damage response pathway in macrophages. C2-formulated TY1 (TY1C2) efficiently packages and protects TY1 against degradative enzymes. In healthy mice, oral TY1C2 was well-tolerated and nontoxic. Oral TY1C2 exhibited disease-modifying bioactivity in 2 models of tissue injury: 1) rat myocardial infarction, where a single oral dose of TY1C2 was cardioprotective, on par with intravenously-delivered TY1; and 2) mouse acute lung injury, where a single dose of TY1C2 attenuated pulmonary inflammation. Mechanistic dissection revealed that TY1C2 is not absorbed into the systemic circulation but is, instead, taken up by intestinal macrophages, namely those of the lamina propria and Peyer's patches. This route of absorption may rationalize why an antisense oligonucleotide against Factor VII, which acts on hepatocytes, is not effective when administered in the C2 formulation. Thus, some (but not all) ncRNA drugs are bioavailable when delivered by mouth. Oral RNA delivery and uptake, relying on uptake via the gastrointestinal immune system, has broad-ranging therapeutic implications.

[Local resection of small intestine neuroendocrine neoplasms (SI-NEN) : Current principles]. / Lokale Resektion von neuroendokrinen Tumoren des Dünndarms (SI-NEN) : Aktuelle Prinzipien.

BACKGROUND: Neuroendocrine tumors of the small bowel (small intestine neuroendocrine neoplasms, SI-NEN) are the most frequent tumors of the small intestine and approximately 30-40% are still surgically treatable with curative intent at the time of diagnosis. Certain surgical principles must be followed for optimal oncological outcomes and good postoperative quality of life. METHODS: Based on international guidelines and own experiences, the locoregional surgical treatment of SI-NENs is presented. RESULTS: Locoregional SI-NENs should always be resected if technically feasible, as only this approach can achieve a long-term cure and even small primary tumors (< 10 mm) often already show lymphatic metastasis. The resectability of SI-NENs and their difficulty depend on the extent of lymphatic metastasis, which should be assessed based on preoperative imaging of the extent around the superior mesenteric artery. Currently, the surgical gold standard for SI-NENs is open surgery with bidigital palpation of the entire small intestine followed by primary tumor resection via small bowel segment resection, right hemicolectomy or ileocecal resection and vessel-sparing, and therefore organ-preserving lymphadenectomy (≥ 8 lymph nodes). The guidelines consider that laparoscopic or robotic approaches are justified only for early stages of SI-NENs. CONCLUSION: Guideline-compliant surgical treatment of locoregional SI-NEN enables recurrence-free long-term survival with good quality of life.

Crude protein content in diets associated with intestinal microbiome and metabolome alteration in Huanjiang mini-pigs during different growth stages.

Introduction: Adequate crude protein (CP) content in diets plays a crucial role in the intestinal health of the animal. This study investigated the impacts of CP content in diets on the intestinal microbiome and metabolome profiles in growing Huanjiang mini-pigs. Methods: A total of 360 pigs with similar body weight (BW) were allocated for three independent feeding trials based on three different BW stages, including (i) 5-10 kg BW, diets consisting of 14, 16, 18, 20, and 22% CP content; (ii) 10-20 kg BW, diets consisting of 12, 14, 16, 18, and 20% CP content; and (iii) 20-30 kg BW, diets consisting of 10, 12, 14, 16, and 18% CP content. These experiments lasted 28, 28, and 26 days, respectively. Results: The results showed that the Shannon and Simpson indices were decreased (p < 0.05) in the ileum of pigs in response to the 14-18% CP compared with the 20% CP content at 5-10 kg BW stage, while diets containing 12 and 14% CP had higher Chao1 (p < 0.05) and Shannon (p = 0.054) indices compared with 18% CP at 20-30 kg BW stage. Compared with the 20% CP, the diet containing 16% CP displayed an increasing trend (p = 0.089) of Firmicutes abundance but had decreased (p = 0.056) Actinobacteria abundance in the jejunum at 5-10 kg BW stage. In addition, a diet containing 16% CP had higher Lactobacillus abundance in the jejunum and ileum compared with the 18, 20, and 22% CP, while had lower Sphingomonas and Pelomonas abundances in the jejunum and Streptococcus abundance in the ileum compared with the diet containing 22% CP (p < 0.05). Diets containing lower CP content altered differential metabolites in the small intestine at the early stage, while higher CP content had less impact. Conclusion: These findings suggest that a diet containing lower CP content (16% CP) may be an appropriate dietary CP content for 5-10 kg Huanjiang mini-pigs, as 16% CP content in diet has shown beneficial impacts on the intestinal microbiome and metabolome profiles at the early growth stage of pigs.

A long journey to the colon: The role of the small intestine microbiota in intestinal disease.

The small intestine represents a complex and understudied gut niche with significant implications for human health. Indeed, many infectious and non-infectious diseases center within the small intestine and present similar clinical manifestations to large intestinal disease, complicating non-invasive diagnosis and treatment. One major neglected aspect of small intestinal diseases is the feedback relationship with the resident collection of commensal organisms, the gut microbiota. Studies focused on microbiota-host interactions in the small intestine in the context of infectious and non-infectious diseases are required to identify potential therapeutic targets dissimilar from those used for large bowel diseases. While sparsely populated, the small intestine represents a stringent commensal bacterial microenvironment the host relies upon for nutrient acquisition and protection against invading pathogens (colonization resistance). Indeed, recent evidence suggests that disruptions to host-microbiota interactions in the small intestine impact enteric bacterial pathogenesis and susceptibility to non-infectious enteric diseases. In this review, we focus on the microbiota's impact on small intestine function and the pathogenesis of infectious and non-infectious diseases of the gastrointestinal (GI) tract. We also discuss gaps in knowledge on the role of commensal microorganisms in proximal GI tract function during health and disease.

Dietary glycine supplementation activates mTOR signaling pathway in tissues of pigs with intrauterine growth restriction.

The mechanistic target of rapamycin (mTOR) cell signaling pathway serves as the central mechanism for the regulation of tissue protein synthesis and growth. We recently reported that supplementing 1% glycine to corn- and soybean meal-based diets enhanced growth performance between weaning and market weights in pigs with intrauterine growth restriction (IUGR). Results of recent studies have revealed an important role for glycine in activating mTOR and protein synthesis in C2C12 muscle cells. Therefore, the present study tested the hypothesis that dietary glycine supplementation enhanced the mTOR cell signaling pathway in skeletal muscle and other tissues of IUGR pigs. At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of two groups: supplementation with either 1% glycine or 1.19% L-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Tissues were obtained from the pigs within 1 wk after the feeding trial ended at 188 d of age to determine the abundances of total and phosphorylated forms of mTOR and its two major downstream proteins: eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and ribosomal protein S6 kinase-1 (p70S6K). Results showed that IUGR decreased (P < 0.05) the abundances of both total and phosphorylated mTOR, 4EBP1, and p70S6K in the gastrocnemius muscle and jejunum. In the longissimus lumborum muscle of IUGR pigs, the abundances of total mTOR did not differ (P > 0.05) but those for phosphorylated mTOR and both total and phosphorylated 4EBP1 and p70S6K were down-regulated (P < 0.05), when compared to NBW pigs. These adverse effects of IUGR in the gastrocnemius muscle, longissimus lumborum muscle, and jejunum were prevented (P < 0.05) by dietary glycine supplementation. Interestingly, the abundances of total or phosphorylated mTOR, 4EBP1, and p70S6K in liver were not affected (P > 0.05) by IUGR or glycine supplementation. Collectively, our findings indicate that IUGR impaired the mTOR cell signaling pathway in tissues of pigs and that adequate glycine intake was crucial for maintaining active mTOR-dependent protein synthesis for the growth and development of skeletal muscle.

High-energy pacing inhibits slow-wave dysrhythmias in the small intestine.

The motility of the gastrointestinal tract is coordinated in part by rhythmic slow waves, and disrupted slow-wave patterns are linked to functional motility disorders. At present, there are no treatment strategies that primarily target slow-wave activity. This study assessed the use of pacing to suppress glucagon-induced slow-wave dysrhythmias in the small intestine. Slow waves in the jejunum were mapped in vivo using a high-resolution surface-contact electrode array in pigs (n = 7). Glucagon was intravenously administered to induce hyperglycemia. Slow-wave propagation patterns were categorized into antegrade, retrograde, collision, pacemaker, and uncoupled activity. Slow-wave characteristics such as period, amplitude, and speed were also quantified. Postglucagon infusion, pacing was applied at 4 mA and 8 mA and the resulting slow waves were quantified spatiotemporally. Antegrade propagation was dominant throughout all stages with a prevalence of 55 ± 38% at baseline. However, glucagon infusion resulted in a substantial and significant increase in uncoupled slow waves from 10 ± 8% to 30 ± 12% (P = 0.004) without significantly altering the prevalence of other slow-wave patterns. Slow-wave frequency, amplitude, and speed remained unchanged. Pacing, particularly at 8 mA, significantly suppressed dysrhythmic slow-wave patterns and achieved more effective spatial entrainment (85%) compared with 4 mA (46%, P = 0.039). This study defined the effect of glucagon on jejunal slow waves and identified uncoupling as a key dysrhythmia signature. Pacing effectively entrained rhythmic activity and suppressed dysrhythmias, highlighting the potential of pacing for gastrointestinal disorders associated with slow-wave abnormalities.NEW & NOTEWORTHY Glucagon was infused in pigs to induce hyperglycemia and the resulting slow-wave response in the intact jejunum was defined in high resolution for the first time. Subsequently, with pacing, the glucagon-induced dysrhythmias were suppressed and spatially entrained for the first time with a success rate of 85%. The ability to suppress slow-wave dysrhythmias through pacing is promising in treating motility disorders that are associated with intestinal dysrhythmias.

RFX6 regulates human intestinal patterning and function upstream of PDX1.

The gastrointestinal (GI) tract is complex and consists of multiple organs with unique functions. Rare gene variants can cause congenital malformations of the human GI tract, although the molecular basis of these has been poorly studied. We identified a patient with compound-heterozygous variants in RFX6 presenting with duodenal malrotation and atresia, implicating RFX6 in development of the proximal intestine. To identify how mutations in RFX6 impact intestinal patterning and function, we derived induced pluripotent stem cells from this patient to generate human intestinal organoids (HIOs). We identified that the duodenal HIOs and human tissues had mixed regional identity, with gastric and ileal features. CRISPR-mediated correction of RFX6 restored duodenal identity. We then used gain- and loss-of-function and transcriptomic approaches in HIOs and Xenopus embryos to identify that PDX1 is a downstream transcriptional target of RFX6 required for duodenal development. However, RFX6 had additional PDX1-independent transcriptional targets involving multiple components of signaling pathways that are required for establishing early regional identity in the GI tract. In summary, we have identified RFX6 as a key regulator in intestinal patterning that acts by regulating transcriptional and signaling pathways.

Digestive bleeding due to jejunal diverticula: diagnosis and management.

A jejunal diverticular haemorrhage is the second most common complication of jejunum diverticula. It can manifest clinically as acute upper gastrointestinal bleeding and is common to imitate acute rectal bleeding. Bleeding is usually associated with or without haemodynamic stability. Its diagnosis is challenging, requiring imaging examinations. Treatment is conservative management or surgery.

Hyperspectral imaging combined with blood oxygen saturation for in vivo analysis of small intestinal necrosis tissue.

Acute mesenteric ischemia (AMI) is a clinically significant vascular and gastrointestinal condition, which is closely related to the blood supply of the small intestine. Unfortunately, it is still challenging to properly discriminate small intestinal tissues with different degrees of ischemia. In this study, hyperspectral imaging (HSI) was used to construct pseudo-color images of oxygen saturation about small intestinal tissues and to discriminate different degrees of ischemia. First, several small intestine tissue models of New Zealand white rabbits were prepared and collected their hyperspectral data. Then, a set of isosbestic points were used to linearly transform the measurement data twice to match the reference spectra of oxyhemoglobin and deoxyhemoglobin, respectively. The oxygen saturation was measured at the characteristic peak band of oxyhemoglobin (560 nm). Ultimately, using the oxygenated hemoglobin reflectance spectrum as the benchmark, we obtained the relative amount of median oxygen saturation in normal tissues was 70.0 %, the IQR was 10.1 %, the relative amount of median oxygen saturation in ischemic tissues was 49.6 %, and the IQR was 14.6 %. The results demonstrate that HSI combined with the oxygen saturation computation method can efficiently differentiate between normal and ischemic regions of the small intestinal tissues. This technique provides a powerful support for internist to discriminate small bowel tissues with different degrees of ischemia, and also provides a new way of thinking for the diagnosis of AMI.

Do Herbal Supplements and Probiotics Complement Antibiotics and Diet in the Management of SIBO? A Randomized Clinical Trial.

Small intestinal bacterial overgrowth (SIBO) arises from dysbiosis in the small intestine, manifesting with abdominal symptoms. This study aims to assess the efficacy of combined antibiotic therapy, herbal supplements, probiotics, and dietary modifications in SIBO management. A total of 179 SIBO-diagnosed patients underwent clinical evaluation and breath testing. Patients were categorized into hydrogen (H2-SIBO) and methane (CH4-SIBO) groups. The control group received standard antibiotic therapy and a low-FODMAP diet, while the intervention group received additional herbal antibiotics, probiotics, and prebiotics. After treatment, both groups exhibited reduced gas levels, particularly in CH4-SIBO. Clinical remission rates were higher in the intervention group, especially in CH4-SIBO cases. Logistic regression analysis showed gas concentrations at diagnosis as significant predictors of treatment success. In conclusion, adjunctive herbal supplements and probiotics did not significantly impact gas levels, but showed potential for clinical improvement, especially in CH4-SIBO.

Duodenal mucosa of untreated celiac disease patients has altered expression of the GAS6 and PROS1 and the negative regulator tyrosine kinase TAM receptors subfamily.

Celiac disease (CD) is an immune-driven disease characterized by tissue damage in the small intestine of genetically-susceptible individuals. We evaluated here a crucial immune regulatory pathway involving TYRO3, AXL, and MERTK (TAM) receptors and their ligands PROS1 and GAS6 in duodenal biopsies of controls and CD patients. We found increased GAS6 expression associated with downregulation of PROS1 and variable TAM receptors levels in duodenum tissue of CD patients. Interestingly, CD3+ lymphocytes, CD68+, CD11c+ myeloid and epithelial cells, showed differential expressions of TAM components comparing CD vs controls. Principal component analysis revealed a clear segregation of two groups of CD patients based on TAM components and IFN signaling. In vitro validation demonstrated that monocytes, T lymphocytes and epithelial cells upregulated TAM components in response to IFN stimulation. Our findings highlight a dysregulated TAM axis in CD related to IFN signaling and contribute to a deeper understanding of the pathophysiology of CD.

Organoid Culture of Different Intestinal Segments from Human and Mouse.

The intestine comprises distinct segments, each characterized by unique cell populations and functions. Intestinal organoids faithfully replicate the cellular composition and functions of the intestine. Over the past decade, the organoid model has garnered considerable attention for its application in investigation of organ development, renewal and functional performance. While the organoid culture systems for mouse small intestine and human large intestine have widely adopted, a comparison summary for different segments of the human or mouse intestine is lacking. In this study, we present a systematically detailed culture methodology for intestinal organoids, encompassing both the small intestine and the large intestine from humans or mice. This method provides a robust in vitro tool for intestinal research, and expands the possible clinical application of organoids.