A felnottkori invaginatiók sebészeti vonatkozásai.

A felnottkori invaginatiók ritkák, klinikai megjelenésük eltér a gyerekkori formáktól. Klinikumuk igen változatos, gyakran atípusos, jellemzo, hogy egy klinikai sejtés nyomán gondolni kell az invaginatio lehetoségére. A kiegészíto vizsgálatok közül kiemelkedo szerep jut a computer tomográfiának (CT), ami magas érzékenységgel és fajlagossággal képes kimutatni a béltraktus invaginatióját. Gyógyításuk az esetek legnagyobb részében sebészi, sokszor csak a mutét során lehetséges felismerni a kiváltó okot. Esetismertetésünkben egy rendkívül ritka, felnottkori, passage-zavart okozó colo-colicus, a bal colonfelet érinto, a colon-flexura lienalis-descendens határra lokalizált invaginatio klinikai jellemzoit, diagnosztikáját és definitív megoldásaként a laparoscoposan asszisztált bal oldali haemicolectomia mutéti megoldását mutatjuk be. Munkánkban összefoglaljuk a felnottkori invaginatiókra vonatkozó kórélettani fogalmakat, diagnosztikai lehetoségeket, a leggyakoribb kiváltó tényezoket és terápiás lehetoségeket.

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Surgical management of duodenal crohn's disease.

BACKGROUND: Operative options for duodenal Crohn's disease include bypass, stricturoplasty, or resection. What factors are associated with operation selection and whether differences exist in outcomes is unknown. METHODS: Patients with duodenal Crohn's disease requiring operative intervention across a multi-state health system were identified. Patient and operative characteristics, short-term surgical outcomes, and the need for future endoscopic or surgical management of duodenal Crohn's disease were analyzed. RESULTS: 40 patients underwent bypass (n = 26), stricturoplasty (n = 8), or resection (n = 6). Median age of diagnosis of Crohn's disease was 23.5 years, and over half of the patients had undergone prior surgery for CD. Operation type varied by the most proximal extent of duodenal involvement. Patients with proximal duodenal CD underwent bypass operations more commonly than those with mid- or distal duodenal disease (p = 0.03). Patients who underwent duodenal stricturoplasty more often required concomitant operations for other sites of small bowel or colonic CD (63%) compared to those who underwent bypass (39%) or resection (33%). No patients required subsequent surgery for duodenal CD at a median follow-up of 2.8 years, but two patients required endoscopic dilation (n = 1 after stricturoplasty, n = 1 after resection). CONCLUSION: Patients who require surgery for duodenal Crohn's disease appear to have an aggressive Crohn's disease phenotype, represented by a younger age of diagnosis and a high rate of prior resection for Crohn's disease. Choice of operation varied by proximal extent of duodenal Crohn's disease.

New insights into starch, lipid, and protein interactions - Colon microbiota fermentation.

Starch, lipids, and proteins are essential biological macromolecules that play a crucial role in providing energy and nutrition to our bodies. Interactions between these macromolecules have been shown to impact starch digestibility. Understanding and controlling starch digestibility is a key area of research. Investigating the mechanisms behind the interactions of these three components and their influence on starch digestibility is of significant practical importance. Moreover, these interactions can result in the formation of resistant starch, which can be fermented by gut microbiota in the colon, leading to various health benefits. While current research has predominantly focused on the digestive properties of starch in the small intestine, there is a notable gap in understanding the colonic microbial fermentation phase of resistant starch. The benefits of fermentation of resistant starch in the colon may outweigh its glucose-lowering effect in the small intestine. Thus, it is crucial to study the fermentation behavior of resistant starch in the colon. This paper investigates the impact of interactions among starch, lipids, and proteins on starch digestion, with a specific focus on the fermentation phase of indigestible carbohydrates in the colon. Furthermore, valuable insights are offered for guiding future research endeavors.

Sarcandra glabra (Thunb.) Nakai alleviates DSS-induced ulcerative colitis by promoting restitution, restoring barrier function, and modulating IL-17/Notch1/FoxP3 pathway in intestinal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcandra glabra is officially named Zhong Jie Feng as a traditional medicine. In the nationality of Yao and Zhuang, it has been used to treat digestive diseases like stomachache and dysentery. Similarly, in Dai nationality, it has been used to treat intestinal diseases like gastric ulcers. However, the effect and mechanism of S. glabra on experimental ulcerative colitis (UC) are known. AIM OF STUDY: The main objective of this study was to investigate the effect and mechanism of S. glabra on experimental UC. MATERIALS AND METHODS: The chemical components in the water extract of S. glabra (ZJF) were analyzed by UPLC-MS/MS method. The HCoEpiC cell line was used to assess the promotive effect on intestinal proliferation and restitution. RAW264.7 cells were used to assess the in vitro anti-inflammatory effect of ZJF. The 3% DSS-induced colitis model was used to evaluate the in vivo effect of ZJF (4.5 g/kg and 9.0 g/kg). Mesalazine (0.5 g/kg) was used as the positive drug. ELISA, RT-qPCR, Western blot, and multiplex immunohistochemical experiments were used to test gene levels in the colon tissue. The H&E staining method was used to monitor the pathological changes of colon tissue. TUNEL assay kit was used to detect apoptosis of epithelial colonic cells. RESULTS: ZJF could alleviate the DSS-caused colitis in colon tissues, showing a comparative effect to that of the positive drug mesalazine. Mechanism study indicated that ZJF could promote normal colonic HCoEpiC cell proliferation and restitution, inhibit overexpression of pro-inflammatory cytokines, restore the M1/M2 ratio, decrease epithelial colonic cell apoptosis, rescue tight junction protein levels, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC. CONCLUSION: Our results indicated that S. glabra can promote intestinal cell restitution, balance immune response, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC.

Hippuric acid alleviates dextran sulfate sodium-induced colitis via suppressing inflammatory activity and modulating gut microbiota.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease associated with metabolic disorder and gut dysbiosis. Decreased abundance of hippuric acid (HA) was found in patients with IBD. HA, metabolized directly from benzoic acid in the intestine and indirectly from polyphenols, serves as a marker of polyphenol catabolism. While polyphenols and benzoic acid have been shown to alleviate intestinal inflammation, the role of HA in this context remains unknown. Herein, we investigated the effects and mechanism of HA on DSS-induced colitis mice. The results revealed that HA alleviated clinical activity and intestinal barrier damage, decreased pro-inflammatory cytokine production. Metagenomic sequencing suggested that HA treatment restored the gut microbiota, including an increase in beneficial gut bacteria such as Adlercreutzia, Eubacterium, Schaedlerella and Bifidobacterium_pseudolongum. Furthermore, we identified 113 candidate genes associated with IBD that are potentially under HA regulation through network pharmacological analyses. 10 hub genes including ALB, IL-6, HSP90AA1, and others were identified using PPI analysis and validated using molecular docking and mRNA expression analysis. Additionally, KEGG analysis suggested that the renin-angiotensin system (RAS), NF-κB signaling and Rap1 signaling pathways were important pathways in the response of HA to colitis. Thus, HA may provide novel biotherapy options for IBD.

Trends in breast, colon, pancreatic, and uterine cancers in women during the COVID-19 pandemic in North Carolina.

IMPORTANCE: The COVID-19 pandemic led to reductions in primary care and cancer screening visits, which may delay detection of some cancers. The impact on incidence has not been fully quantified. We examined change in cancer incidence to determine how the COVID-19 pandemic may have altered the characteristics of cancers diagnosed among women. METHODS: This study included female patients aged ≥18 years and diagnosed with breast (n = 9489), colon (n = 958), pancreatic (n = 669), or uterine (n = 1991) cancer at three hospitals in North Carolina. Using interrupted time series, we compared incidence of cancers diagnosed between March 2020 and November 2020 (during pandemic) with cancers diagnosed between January 2016 and February 2020 (pre-pandemic). RESULTS: During the pandemic, incidence of breast and uterine cancers was significantly lower than expected compared to pre-pandemic (breast-18%, p = 0.03; uterine -20%, p = 0.05). Proportions of advanced pathologic stage and hormone receptor-negative breast cancers, and advanced clinical stage and large size uterine cancers were more prevalent during the pandemic. No significant changes in incidence were detected for pancreatic (-20%, p = 0.08) or colon (+14%, p = 0.30) cancers. CONCLUSION AND RELEVANCE: In women, the COVID-19 pandemic resulted in a significant reduction in the incidence of breast and uterine cancers, but not colon or pancreatic cancers. A change in the proportion of poor prognosis breast and uterine cancers suggests that some cancers that otherwise would have been diagnosed at an earlier stage will be detected in later years. Continued analysis of long-term trends is needed to understand the full impact of the pandemic on cancer incidence and outcomes.

Soy Protein Concentrate Diets Inversely Affect LPS-Binding Protein Expression in Colon and Liver, Reduce Liver Inflammation, and Increase Fecal LPS Excretion in Obese Zucker Rats.

Dietary soy protein and soy isoflavones have anti-inflammatory properties. Previously, we reported that feeding soy protein concentrate diet (SPC) with low or high isoflavone (LIF or HIF) to young (seven-week-old) obese (fa/fa) Zucker rats inhibits lipopolysaccharide (LPS) translocation and decreases liver inflammation compared to a casein control (CAS) diet. The current study investigated whether SPC-LIF and SPC-HIF diets would reduce liver inflammation in adult obese Zucker rats fed a CAS diet. A total of 21 six-week-old male obese (fa/fa) Zucker rats were given CAS diet for 8 weeks to develop obesity then randomly assigned to CAS, SPC-LIF, or SPC-HIF (seven rats/group) diet for an additional 10 weeks. The expression of LPS-translocation, inflammation, and intestinal permeability markers were quantified by qPCR in liver, visceral adipose tissue (VAT), and colon. LPS concentration was determined in both the colon content and fecal samples by a Limulus amebocyte lysate (LAL) test. SPC-LIF and SPC-HIF diets significantly decreased liver LPS-binding protein (LBP) expression compared to CAS diet (p < 0.01 and p < 0.05, respectively). SPC-HIF diet also significantly decreased liver MCP-1 and TNF-α expression (p < 0.05) and had a trend to decrease liver iNOS expression (p = 0.06). In the colon, SPC-HIF diet significantly increased LBP expression compared to CAS diet (p < 0.05). When samples from all three groups were combined, there was a negative correlation between colon LBP expression and liver LBP expression (p = 0.046). SPC diets did not alter the expression of intestinal permeability markers (i.e., occludin, claudin 3, and zonula occludens-1) in the colon or inflammation markers (i.e., TNF-α and iNOS) in VAT or the colon. LPS levels in the colon content did not differ between any groups. Fecal LPS levels were significantly higher in the SPC-LIF and SPC-HIF groups compared to the CAS group (p < 0.01). In conclusion, SPC, particularly SPC with HIF, reduces liver LBP expression and inflammation makers (i.e., TNF-α and MCP-1 expression) in adult obese Zucker rats, likely by reducing LPS translocation.

Torsion of the spiral colon in cattle- a retrospective analysis of 58 cases.

BACKGROUND: Torsion of the spiral colon (TSC) describes twisting of the spiral colon around its mesentery. The present study reviewed the medical records of 58 cows and heifers with TSC and described the findings, treatment and outcome. RESULTS: All cases had an abnormal general condition, and the main vital sign abnormalities were tachycardia (72.4%), tachypnoea (67.2%) and decreased rectal temperature (51.8%). Signs of colic were seen in 62.1% of the cows. The most common intestinal abnormalities were an empty or almost empty rectum (96.6%), reduced or absent rumen motility (93.2%), positive ballottement and/or percussion and simultaneous auscultation on the right side of the abdomen (87.9%), reduced or absent intestinal motility (84.5%) and dilatation of the large intestines (spiral colon and/or caecum, 70.7%) diagnosed by transrectal palpation. The main biochemical changes were hypermagnesaemia (70.8%), hypocalcaemia (70.8%), and acidosis (66.7%). Haemoconcentration was found in 63.8%. The main ultrasonographic findings were reduced to absent small intestinal motility (83.3%), dilated small intestines (69.6%) and ascites (66.7%). The spiral colon was dilated in 44.0% of the cows and the caecum in 24.0%. The actual site of torsion could not be visualised. Based on the clinical findings, TSC was diagnosed in 22.4% and caecal dilatation in 50.0% of the cows. A tentative diagnosis of small intestinal ileus was made in another 10.3% of the cows, and a definitive diagnosis of small intestinal ileus in 17.3%. Fifty-three cows underwent right flank laparotomy, and the TSC could be reduced in 26. Twenty-six of the 58 (44.8%) cows were discharged and 32 (55.2%) were euthanased before, during or after surgery. CONCLUSIONS: Acute illness, a sparse amount of faeces in the rectum and dilated spiral colon and caecum are characteristic findings of TSC. The final diagnosis often relies on the surgical or postmortem findings. Cattle with TSC should be treated surgically without delay. The prognosis is guarded with a survival rate of 44.8%.

Rab7-dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis.

Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability, and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7-dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.

Metabolomics approach for predicting stomach and colon contents in dead Arctocephalus pusillus pusillus, Arctocephalus tropicalis, Lobodon carcinophaga and Ommatophoca rossii from sub-Antarctic region.

The dietary habits of seals play a pivotal role in shaping management and administration policies, especially in regions with potential interactions with fisheries. Previous studies have utilized various methods, including traditional approaches, to predict seal diets by retrieving indigestible prey parts, such as calcified structures, from intestines, feces, and stomach contents. Additionally, methods evaluating nitrogen and stable isotopes of carbon have been employed. The metabolomics approach, capable of quantifying small-scale molecules in biofluids, holds promise for specifying dietary exposures and estimating disease risk. This study aimed to assess the diet composition of five seal species-Arctocephalus pusillus pusillus, Lobodon carcinophaga, Ommatophoca rossii, and Arctocephalus tropicalis 1 and 2-by analyzing stomach and colon contents collected from stranded dead seals at various locations. Metabolite concentrations in the seal stomach and colon contents were determined using Nuclear Magnetic Resonance Spectroscopy. Among the colon and stomach contents, 29 known and 8 unknown metabolites were identified. Four metabolites (alanine, fumarate, lactate, and proline) from stomach contents and one metabolite (alanine) from colon contents showed no significant differences between seal species (p>0.05). This suggests that traces of these metabolites in the stomach and colon contents may be produced by the seals' gut microbiome or derived from other animals, possibly indicating reliance on fish caught at sea. Despite this insight, the cause of death for stranded seals remains unclear. The study highlights the need for specific and reliable biomarkers to precisely indicate dietary exposures across seal populations. Additionally, there is a call for the development of relevant metabolite and disease interaction networks to explore disease-related metabolites in seals. Ultimately, the metabolomic method employed in this study reveals potential metabolites in the stomach and colon contents of these seal species.

Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth.

Genome-wide analysis identifies MYH11 compound heterozygous variants leading to visceral myopathy corresponding to late-onset form of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Megacystis-microcolon-hypoperistalsis-syndrome (MMIHS) is a rare and early-onset congenital disease characterized by massive abdominal distension due to a large non-obstructive bladder, a microcolon and decreased or absent intestinal peristalsis. While in most cases inheritance is autosomal dominant and associated with heterozygous variant in ACTG2 gene, an autosomal recessive transmission has also been described including pathogenic bialellic loss-of-function variants in MYH11. We report here a novel family with visceral myopathy related to MYH11 gene, confirmed by whole genome sequencing (WGS). WGS was performed in two siblings with unusual presentation of MMIHS and their two healthy parents. The 38 years-old brother had severe bladder dysfunction and intestinal obstruction, whereas the 30 years-old sister suffered from end-stage kidney disease with neurogenic bladder and recurrent sigmoid volvulus. WGS was completed by retrospective digestive pathological analyses. Compound heterozygous variants of MYH11 gene were identified, associating a deletion of 1.2 Mb encompassing MYH11 inherited from the father and an in-frame variant c.2578_2580del, p.Glu860del inherited from the mother. Pathology analyses of the colon and the rectum revealed structural changes which significance of which is discussed. Cardiac and vascular assessment of the mother was normal. This is the second report of a visceral myopathy corresponding to late-onset form of MMIHS related to compound heterozygosity in MYH11; with complete gene deletion and a hypomorphic allele in trans. The hypomorphic allele harbored by the mother raised the question of the risk of aortic disease in adults. This case shows the interest of WGS in deciphering complex phenotypes, allowing adapted diagnosis and genetic counselling.

Non-malignant left colon emergency surgery: evaluation of factors affecting clinical outcomes and complications.

BACKGROUND: Emergency colorectal resections hold a significant position in general surgical practice, and pathologies of the left colon are relatively common. This study was conducted to assess the outcomes of isolated left colon surgeries with benign etiologies, drawing on clinicopathological and biochemical data. METHODS: We carried out a retrospective review and statistical analysis of demographic, clinical, and laboratory data of patients who underwent left colon surgery at the general surgery clinic of a tertiary care hospital, excluding those with malignancy-related emergencies, from January 2017 to January 2022. RESULTS: The average age of the 48 patients in the study was 56.9±16.4 years. Complicated acute diverticulitis was the most frequent indication for emergency surgery (n=19, 39.6%). The Hartmann procedure was the surgical technique most often employed (n=30, 62.5%). The rates of postoperative morbidity and mortality within 30 days were 27.1% and 8.3%, respectively. Increased postoperative morbidity was linked to advanced age (mean 65.4±15.8 vs. 53.8±15.7, p=0.028), the preoperative administration of vasopressors, lower platelet counts, hypoalbuminemia (<3 mg/dl), and azotemia (blood urea nitrogen >20 mg/dl). There was no statistically significant correlation between comorbidities, American Society of Anesthesiologists (ASA) scores, surgical methods, or other clinical data and postoperative outcomes. CONCLUSION: For emergency colorectal surgery pertaining to left colon pathologies, it is critical to conduct a comprehensive evaluation in the perioperative period, especially for elderly and hypotensive patients with renal function abnormalities and for those requiring vasopressors.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS): challenges in diagnosis and management.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare, congenital functional intestinal obstruction, characterised by megacystis (bladder distention in the absence of mechanical obstruction), microcolon and intestinal hypoperistalsis (dysmotility).We are reporting a case of a female child with normal antenatal course who presented with recurrent episodes of abdominal distension since the second day of life and underwent negative exploratory laparotomy on multiple occasions. She also had urinary retention with a grossly distended bladder, requiring drainage by clean intermittent catheterisation. Surgical procedures for bowel decompression, including gastrostomy and ileostomy, were carried out without success. Genetic analysis revealed a mutation in the human smooth muscle (enteric) gamma-actin gene (ACTG2 gene), clinching the diagnosis of MMIHS. The patient was managed with parenteral nutrition and prokinetic medications and tolerated jejunostomy feeds for a brief period before she succumbed to the illness.Female neonates or infants presenting with abdominal distension and dilated urinary tract should be investigated for MMIHS early on. A timely diagnosis will enable the early involvement of a multidisciplinary team to provide the best options available for management.

Levels of lipid-derived gut microbial metabolites differ among plant matrices in an in vitro model of colon fermentation.

This study explored differences in microbial lipid metabolites among sunflower seeds, soybeans, and walnuts. The matrices were subjected to in vitro digestion and colonic fermentation. Defatted digested materials and fiber/phenolics extracted therefrom were added to sunflower oil (SO) and also fermented. Targeted and untargeted lipidomics were employed to monitor and tentatively identify linoleic acid (LA) metabolites. Walnut fermentation produced the highest free fatty acids (FFAs), LA, and conjugated LAs (CLAs). Defatted digested walnuts added to SO boosted FFAs and CLAs production; the addition of fibre boosted CLAs, whereas the addition of phenolics only increased 9e,11z-CLA and 10e,12z-CLA. Several di-/tri-hydroxy-C18-FAs, reported as microbial LA metabolites for the first time, were annotated. Permutational multivariate analysis of variance indicated significant impacts of food matrix presence and type on lipidomics and C18-FAs. Our findings highlight how the food matrices affect CLA production from dietary lipids, emphasizing the role of food context in microbial lipid metabolism.

The Role of Gut-derived Short-Chain Fatty Acids in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic condition affecting the central nervous system (CNS), where the interplay of genetic and environmental factors influences its pathophysiology, triggering immune responses and instigating inflammation. Contemporary research has been notably dedicated to investigating the contributions of gut microbiota and their metabolites in modulating inflammatory reactions within the CNS. Recent recognition of the gut microbiome and dietary patterns as environmental elements impacting MS development emphasizes the potential influence of small, ubiquitous molecules from microbiota, such as short-chain fatty acids (SCFAs). These molecules may serve as vital molecular signals or metabolic substances regulating host cellular metabolism in the intricate interplay between microbiota and the host. A current emphasis lies on optimizing the health-promoting attributes of colonic bacteria to mitigate urinary tract issues through dietary management. This review aims to spotlight recent investigations on the impact of SCFAs on immune cells pivotal in MS, the involvement of gut microbiota and SCFAs in MS development, and the considerable influence of probiotics on gastrointestinal disruptions in MS. Comprehending the gut-CNS connection holds promise for the development of innovative therapeutic approaches, particularly probiotic-based supplements, for managing MS.

Short-chain fatty acid-producing bacterial strains attenuate experimental ulcerative colitis by promoting M2 macrophage polarization via JAK/STAT3/FOXO3 axis inactivation.

BACKGROUND: Patients with inflammatory bowel disease (IBD), dysbiosis, and immunosuppression who receive fecal microbiota transplantation (FMT) from healthy donors are at an increased risk of developing bacteremia. This study investigates the efficacy of a mixture of seven short-chain fatty acid (SCFA)-producing bacterial strains (7-mix), the resulting culture supernatant mixture (mix-sup), and FMT for treating experimental ulcerative colitis (UC) and evaluates underlying mechanisms. METHODS: Utilizing culturomics, we isolated and cultured SCFA-producing bacteria from the stool of healthy donors. We used a mouse model of acute UC induced by dextran sulfate sodium (DSS) to assess the effects of 7-mix, mix-sup, and FMT on intestinal inflammation and barrier function, microbial abundance and diversity, and gut macrophage polarization by flow cytometry, immunohistochemistry, 16S rRNA gene sequencing, and transwell assays. RESULTS: The abundance of several SCFA-producing bacterial taxa decreased in patients with UC. Seven-mix and mix-sup suppressed the inflammatory response and enhanced intestinal mucosal barrier function in the mouse model of UC to an extent similar to or superior to that of FMT. Moreover, 7-mix and mix-sup increased the abundance of SCFA-producing bacteria and SCFA concentrations in colitic mice. The effects of these interventions on the inflammatory response and gut barrier function were mediated by JAK/STAT3/FOXO3 axis inactivation in macrophages by inducing M2 macrophage polarization in vivo and in vitro. CONCLUSIONS: Our approach provides new opportunities to rationally harness live gut probiotic strains and metabolites to reduce intestinal inflammation, restore gut microbial composition, and expedite the development of safe and effective treatments for IBD.

Disease clearance in ulcerative colitis: A new therapeutic target for the future.

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression. This has fueled the identification of molecular targets, resulting in a rapidly expanding therapeutic armamentarium. Subsequently, management strategies have evolved from symptomatic resolution to well-defined objective endpoints, including clinical remission, endoscopic remission and mucosal healing. While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications, studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures. Current recommendations lack consideration of histological healing. The simultaneous achievement of clinical, endoscopic, and histologic remission has not been fully investigated. This has laid the groundwork for a novel therapeutic outcome termed disease clearance (DC). This article summarizes the concept of DC and its current evidence.