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1.
Pediatr Surg Int ; 40(1): 97, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38581576

ABSTRACT

PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.


Subject(s)
Intestinal Diseases , Intestinal Failure , Liver Diseases , Liver Failure , Humans , Child , Fat Emulsions, Intravenous/therapeutic use , Parenteral Nutrition , Retrospective Studies , Intestinal Diseases/drug therapy , Liver Diseases/complications , Liver Failure/complications , Soybean Oil/therapeutic use , Weight Gain , Fish Oils
2.
Nutrition ; 122: 112372, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38428218

ABSTRACT

OBJECTIVES: Aging and excessive fat intake may additively induce dysbiosis of the gut microbiota and intestinal inflammatory damage. Here, we analyzed microbiota dysbiosis and intestinal injury in high-fat diet-loaded senescence-accelerated mice (SAMP8). Additionally, we examined whether treatment with molecular hydrogen could improve the intestinal environment. METHODS: SAMP8 and SAMR1 (control) mice were first fed a normal diet (ND) or high-fat diet (HFD) for 10 wk (n = 10 each group). Subsequently, HFD was supplemented with a placebo jelly or hydrogen-rich jelly (HRJ) for 4 wk. After treatment, isolated small intestinal tissues were used for hematoxylin and eosin staining, immunofluorescence staining, and thiobarbituric acid reactive substances (TBARS) assay. Furthermore, we analyzed alterations in the microbiota composition in cecal feces using 16S rRNA gene analysis for microbiota profiling. Statistical analyses were performed using unpaired Student's t tests or one-way analysis of variance and Tukey's post hoc test for multiple comparisons. RESULT: HFD feeding reduced the expression of caudal-related homeobox transcription factor 2 (CDX2) and 5-bromo-2'-deoxyuridine (BrdU) and enhanced malondialdehyde (MDA) levels in the small intestine of SAMP8. HRJ treatment improved the reduction in CDX2 and BrdU and enhanced MDA levels. We performed a sequence analysis of the gut microbiota at the genus level and identified 283 different bacterial genera from the 30 samples analyzed in the study. Among them, Parvibacter positively correlated with both HFD intake and aging, whereas 10 bacteria, including Anaerofustis, Anaerosporobacter, Butyricicoccus, and Ruminococcus were negatively correlated with both HFD and aging. HRJ treatment increased Lactinobactor and decreased Akkermansia, Gracilibacter, and Marvinbryantia abundance. CONCLUSION: Our findings suggest that treatment with molecular hydrogen may affect microbiota profiling and suppress intestinal injury in HFD-loaded SAMP8.


Subject(s)
Diet, High-Fat , Intestinal Diseases , Mice , Animals , Diet, High-Fat/adverse effects , Dysbiosis/microbiology , RNA, Ribosomal, 16S/genetics , Bromodeoxyuridine/therapeutic use , Intestine, Small/metabolism , Intestinal Diseases/drug therapy , Intestinal Diseases/etiology , Mice, Inbred C57BL
3.
Poult Sci ; 103(5): 103586, 2024 May.
Article in English | MEDLINE | ID: mdl-38442474

ABSTRACT

Intestinal inflammation is a primary contributor to poor growth performance during poultry production. Chlorogenic acid (CGA) is a natural phenolic acid that exhibits superior anti-inflammatory activity and improved intestinal health. To investigate the protective effects and molecular mechanisms of CGA during intestinal inflammation in lipopolysaccharide (LPS)-challenged broilers, we randomly divided 288 one-day-old male Cobb broilers into 4 groups: a control group fed a basal diet (CON group), a basal diet + LPS group (LPS group), and 2 basal diet groups fed 500 or 750 mg/kg CGA + LPS (CGA_500 or CGA_750 groups). Broilers were injected with LPS or saline at 15, 17, 19, and 21 d old. Chlorogenic acid supplementation improved the growth performance of LPS-challenged broilers by increasing average daily gain (ADG) and reducing feed/gain (F/G) ratios (P < 0.05). CGA also improved intestinal barrier function in LPS-challenged boilers by enhancing jejunum morphology and integrity, decreasing intestinal permeability, and increasing occludin 3, zonula occludens-1, and mucin 2 expression (P < 0.05). CGA supplementation also improved systemic and jejunum antioxidant capacity by significantly enhancing glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities (P < 0.05), and reducing malonaldehyde (MDA) and protein carbonyl (PCO) levels (P < 0.05). Chlorogenic acid supplementation reduced systemic and jejunum pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, and IL-12) and increased anti-inflammatory cytokines (IL-10) in LPS-challenged broilers (P < 0.05) by inhibiting the toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway (P < 0.05). In addition, the protective effects of CGA toward intestinal inflammation and apoptosis appeared to be correlated with inhibited endoplasmic reticulum (ER) stress (P < 0.05). In summary, CGA supplementation improved intestinal morphology and integrity by inhibiting TLR4/NF-κB and ER stress pathways, which potentially reduced oxidative stress and inflammation, and ultimately improved the growth performance of LPS-challenged broilers.


Subject(s)
Chickens , Chlorogenic Acid , Dietary Supplements , Endoplasmic Reticulum Stress , Lipopolysaccharides , NF-kappa B , Poultry Diseases , Animals , Chlorogenic Acid/administration & dosage , Chlorogenic Acid/pharmacology , Lipopolysaccharides/pharmacology , Male , NF-kappa B/metabolism , Poultry Diseases/chemically induced , Poultry Diseases/drug therapy , Endoplasmic Reticulum Stress/drug effects , Dietary Supplements/analysis , Diet/veterinary , Inflammation/veterinary , Inflammation/drug therapy , Inflammation/chemically induced , Random Allocation , Animal Feed/analysis , Intestines/drug effects , Intestines/pathology , Intestinal Diseases/veterinary , Intestinal Diseases/chemically induced , Intestinal Diseases/drug therapy , Intestinal Diseases/prevention & control , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/administration & dosage
4.
Curr Microbiol ; 81(2): 55, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38191691

ABSTRACT

In recent years, commercial use of antibiotic growth promoter (AGP) has restrictions due to drug resistance against intestinal pathogenic bacteria: Escherichia coli, Salmonella, and Clostridium perfringens. Currently there is no single non-antibiotic treatment approach that is effective against intestinal illnesses in broiler chicken. Hence, present study aimed to analyze efficacy of blend of natural antimicrobial substances (probiotics, prebiotics, organic acids, and essential oils blend named as AGPR) as replacers of AGPs (BMD and CTC) for promoting growth and controlling bacterial diseases in aforementioned three microbes challenged broiler chickens. Effects of treatments (5) and microbes (3) on growth and health performances in experimental birds were analyzed using two factorial ANOVA. Health performance like pathogen loads, morbidity and mortality was considerably reduced by AGPR. Similarly small intestine villi morphometry, nutrition utilization, serum immune response, and carcass yield, was improved significantly by AGPR equivalent to AGPs. Further, growth performance like body weight gain, feed efficiency was also improved by AGPR compared to control but, non-significantly. Among three microbes, E. coli infections had higher morbidity and mortality rates. It was concluded that AGPR blend could be used to improve growth and control the intestinal bacterial infections in broiler chickens as an alternative for AGPs.


Subject(s)
Anti-Infective Agents , Bacterial Infections , Escherichia coli Infections , Intestinal Diseases , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Chickens , Escherichia coli , Intestinal Diseases/drug therapy , Intestinal Diseases/veterinary , Escherichia coli Infections/drug therapy , Escherichia coli Infections/veterinary
5.
BMC Gastroenterol ; 23(1): 449, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38114956

ABSTRACT

BACKGROUND: Intestinal Behçet's disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. METHODS: This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçet's disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). RESULTS: A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953-0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). CONCLUSION: Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs.


Subject(s)
Behcet Syndrome , Intestinal Diseases , Humans , Adalimumab/adverse effects , Behcet Syndrome/complications , Behcet Syndrome/drug therapy , Intestines , Infliximab , Intestinal Diseases/drug therapy , Intestinal Diseases/chemically induced
6.
Drug Des Devel Ther ; 17: 3803-3831, 2023.
Article in English | MEDLINE | ID: mdl-38155743

ABSTRACT

Dysregulation of the gut microbial ecosystem (GME) (eg, alterations in the gut microbiota, gut-derived metabolites, and gut barrier) may contribute to the onset and progression of extra-intestinal diseases. Previous studies have found that Traditional Chinese Medicine herbs (TCMs) play an important role in manipulating the GME, but a prominent obstacle in current TCM research is the causal relationship between GME and disease amelioration. Encouragingly, co-housing and fecal microbiota transplantation (FMT) provide evidence-based support for TCMs to treat extra-intestinal diseases by targeting GME. In this review, we documented the principles, operational procedures, applications and limitations of the key technologies (ie, co-housing and FMT); furthermore, we provided evidence that TCM works through the GME, especially the gut microbiota (eg, SCFA- and BSH-producing bacteria), the gut-derived metabolites (eg, IS, pCS, and SCFAs), and intestinal barrier to alleviate extra-intestinal diseases. This will be beneficial in constructing microecological pathways for TCM treatment of extra-intestinal diseases in the future.


Subject(s)
Gastrointestinal Microbiome , Intestinal Diseases , Humans , Fecal Microbiota Transplantation/methods , Gastrointestinal Microbiome/physiology , Housing , Intestinal Diseases/drug therapy
7.
N Engl J Med ; 389(18): 1649-1659, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37913505

ABSTRACT

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).


Subject(s)
Angiodysplasia , Gastrointestinal Hemorrhage , Hematologic Agents , Intestinal Diseases , Intestine, Small , Thalidomide , Humans , Angiodysplasia/complications , Angiodysplasia/drug therapy , China , Double-Blind Method , Gastrointestinal Hemorrhage/drug therapy , Gastrointestinal Hemorrhage/etiology , Thalidomide/administration & dosage , Thalidomide/adverse effects , Thalidomide/therapeutic use , Treatment Outcome , Intestinal Diseases/complications , Intestinal Diseases/drug therapy , Recurrence , Intestine, Small/blood supply , Administration, Oral , Hematologic Agents/administration & dosage , Hematologic Agents/adverse effects , Hematologic Agents/therapeutic use
8.
Expert Rev Gastroenterol Hepatol ; 17(10): 1011-1029, 2023.
Article in English | MEDLINE | ID: mdl-37796746

ABSTRACT

INTRODUCTION: Intestinal diseases, a leading global cause of mortality and morbidity, carry a substantial socioeconomic burden. Small and large intestines play pivotal roles in gastrointestinal physiology and food digestion. Pathological conditions, such as gut dysbiosis, inflammation, cancer, therapy-related complications, ulcers, and ischemia, necessitate the urgent exploration of safe and effective complementary therapeutic strategies for optimal intestinal health. AREAS COVERED: This article evaluates the potential therapeutic effects of melatonin, a molecule with a wide range of physiological actions, on intestinal diseases including inflammatory bowel disease, irritable bowel syndrome, colon cancer, gastric/duodenal ulcers and other intestinal disorders. EXPERT OPINION: Due to anti-inflammatory and antioxidant properties as well as various biological actions, melatonin could be a therapeutic option for improving digestive disorders. However, more researches are needed to fully understand the potential benefits and risks of using melatonin for digestive disorders.


Subject(s)
Gastrointestinal Diseases , Intestinal Diseases , Irritable Bowel Syndrome , Melatonin , Humans , Melatonin/adverse effects , Intestinal Diseases/drug therapy , Gastrointestinal Diseases/therapy , Antioxidants/adverse effects
9.
Food Funct ; 14(16): 7705-7717, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37547959

ABSTRACT

During weaning, piglets are susceptible to intestinal injuries caused by a range of infections, which result in serious economic losses for pig producers. Caffeic acid (CA) is a plant-derived phenolic acid that exhibits potential as a dietary supplement for enhancing intestinal health. There is, however, limited information available about the potential benefits of CA supplementation on intestinal injury and growth performance in piglets. A 28-day study was conducted to examine the effectiveness of CA supplementation in protecting against intestinal injury induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS) in piglets. Twenty-four piglets (7.43 ± 0.79 kg body weight; Duroc × Landrace × Large White; barrows) were randomly divided into 4 groups: the control group, the LPS group, the LPS + CA group, and the CA group. Piglets were administered with LPS or saline on d21 and d28 of the experiment. Supplementation with CA improved intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, as well as increasing the expression of Claudin-1 and ZO-1. Meanwhile, CA supplementation improved the systemic and colonic inflammation responses, oxidative stress, and apoptosis induced by LPS. CA supplementation improved the alpha diversity and structure of the intestinal microbiota by increasing the abundance of beneficial microbiota. Additionally, it was found that it improves metabolic disorders of colonic bile acids (BAs) and short-chain fatty acids (SCFAs) in LPS-challenged piglets, including an increase in primary BAs and isovalerate. In conclusion, CA supplementation could enhance intestinal integrity and barrier function by modifying intestinal microbiota and its metabolites, which could lead to a reduction in inflammatory responses and oxidative stress and ultimately enhanced growth performance in piglets.


Subject(s)
Gastrointestinal Microbiome , Intestinal Diseases , Swine , Animals , Lipopolysaccharides/adverse effects , Dietary Supplements/analysis , Intestines , Intestinal Diseases/drug therapy , Intestinal Diseases/veterinary , Intestinal Diseases/chemically induced , Weaning
10.
Korean J Intern Med ; 38(5): 661-671, 2023 09.
Article in English | MEDLINE | ID: mdl-37491721

ABSTRACT

BACKGROUND/AIMS: The short- and long-term effects of adalimumab (ADA) on Korean patients with intestinal Behcet's disease (BD) for remain unclear. Therefore, a multicenter study was performed to evaluate the efficacy and safety of ADA in Korean patients with intestinal BD in a real-world setting. METHODS: The medical records of 67 patients with BD prescribed ADA between January 2012 and December 2020 at five referral centers in Korea were retrospectively analyzed and the safety and efficacy of ADA within 52 weeks were assessed. To evaluate the clinical efficacy of ADA, the Disease Activity Index for Intestinal BD (DAIBD) and representative blood biochemical markers were compared at 0, 12, 24, and 52 weeks of ADA treatment. RESULTS: During the follow-up period of 52 weeks, 46 patients continued ADA treatment. The cumulative drug survival rate was 83.5%. The DAIBD score decreased over the study period (p < 0.001). Moreover, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum albumin levels significantly improved at 12, 24, and 52 weeks of ADA treatment (all, p <0.05). CONCLUSION: As ADA is effective for refractory intestinal BD with few safety concerns in real-world situations, it is a potential treatment option for Korean patients with intestinal BD.


Subject(s)
Behcet Syndrome , Intestinal Diseases , Humans , Adalimumab/adverse effects , Behcet Syndrome/diagnosis , Behcet Syndrome/drug therapy , Retrospective Studies , Intestinal Diseases/diagnosis , Intestinal Diseases/drug therapy , Treatment Outcome , Republic of Korea
11.
Curr Opin Clin Nutr Metab Care ; 26(5): 449-454, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37421385

ABSTRACT

Short bowel syndrome (SBS) is a rare condition defined as a reduced residual functional small intestinal length to less than 200 cm often resulting from extensive intestinal resection, and can lead to chronic intestinal failure (CIF). Patients with SBS-CIF are unable to absorb sufficient nutrients or fluids to maintain metabolic homeostasis through oral or enteral intake and require long-term parenteral nutrition and/or fluids and electrolytes. However, complications may arise from both SBS-IF and life-sustaining intravenous support, such as intestinal failure-associated liver disease (IFALD), chronic renal failure, metabolic bone disease and catheter-related complications. An interdisciplinary approach is required to optimize intestinal adaptation and decrease complications. In the last two decades, glucagon-like peptide 2 (GLP-2) analogs have sparked pharmacological interest as a potential disease-modifying therapy for SBS-IF. Teduglutide (TED) is the first developed and marketed GLP-2 analog for SBS-IF. It is approved in the United States, Europe, and Japan for use in adults and children with SBS-IF who are intravenous supplementation dependent. This article discusses the indications, candidacy criteria and results of the use of TED in patients with SBS.


Subject(s)
Intestinal Diseases , Intestinal Failure , Short Bowel Syndrome , Adult , Child , Humans , Gastrointestinal Agents/therapeutic use , Intestine, Small , Intestines , Short Bowel Syndrome/drug therapy , Intestinal Diseases/drug therapy , Chronic Disease , Glucagon-Like Peptide 2/therapeutic use
12.
Medicine (Baltimore) ; 102(25): e34118, 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37352037

ABSTRACT

RATIONALE: Tocilizumab, a humanized anti-interleukin-6 (IL-6) receptor monoclonal antibody, is used for the treatment of adult-onset Still disease (AOSD). Despite its efficacy in many clinical situations, concerns have been raised regarding intestinal mucosal injury in patients receiving tocilizumab. PATIENT CONCERNS: A 64-year-old woman with a history of AOSD was admitted to our hospital with hematochezia. She had AOSD for 15 years and underwent treatment with biweekly tocilizumab 9 months prior to admission. Colonoscopy revealed a large punched-out ulcer in the terminal ileum. On pathological evaluation, nonspecific enteritis with lymphocytes and eosinophils were seen. Based on the location and shape of the lesion, we suspected intestinal Behçet's disease. However, the ulcer reduced in size over time by discontinuation of tocilizumab without additional drug treatment, indicating that it was a drug-induced ulcer. DIAGNOSIS: The patient was diagnosed with tocilizumab-induced small intestinal ulcer. INTERVENTIONS: The patient treated with the discontinuation of tocilizumab. OUTCOMES: The discontinuation of tocilizumab resulted in ulcer scarring. There was no recurrence of hematochezia. LESSONS: Tocilizumab can cause deep ulcerative lesions in the terminal ileum, which may resemble intestinal Behçet's disease. It is important to continuously monitor abdominal symptoms during tocilizumab therapy and aggressively perform colonoscopy when hematochezia or abdominal pain is observed.


Subject(s)
Behcet Syndrome , Intestinal Diseases , Adult , Female , Humans , Middle Aged , Behcet Syndrome/drug therapy , Ulcer/chemically induced , Ulcer/diagnosis , Ulcer/drug therapy , Intestinal Diseases/chemically induced , Intestinal Diseases/diagnosis , Intestinal Diseases/drug therapy , Antibodies, Monoclonal/therapeutic use , Ileum/pathology , Gastrointestinal Hemorrhage/drug therapy
13.
Biomed Pharmacother ; 163: 114860, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37196540

ABSTRACT

The antibiotic-induced intestinal injury (AIJ) is associated with diarrhoea and gastrointestinal discomfort. However, the pathological intestinal mechanisms and related side effects associated with antibiotic use/misuse may be counteracted by probiotics. This study aims to evaluate the effect and the protective mechanisms of a probiotic formulation containing Alkalihalobacillus clausii (formerly Bacillus clausii; BC) spores in an experimental model of AIJ. C57/Bl6J mice were orally challenged with a high dose of ceftriaxone for five days along with BC treatment which lasted up to the 15th day. Our results showed the beneficial effect of the probiotic in preserving colonic integrity and limiting tissue inflammation and immune cell infiltration in AIJ mice. BC increased tight junction expression and regulated the unbalanced production of colonic pro- and anti-inflammatory cytokines, converging toward the full resolution of the intestinal damage. These findings were supported by the histological evaluation of the intestinal mucosa, suggesting a potential restoration of mucus production. Notably, BC treatment increased gene transcription of the secretory products responsible for epithelium repair and mucus synthesis and normalized the expression of antimicrobial peptides involved in immune activation. Reconstruction of complex and diverse gut microbiota in antibiotic-induced dysbiosis was recorded upon BC supplementation. Specifically, the expansion of A. clausii, Prevotella rara and Eubacterium ruminatium drove intestinal microbiota rebalance by primarily impacting Bacteroidota members. Taken together, our data indicate that BC administration alleviates AIJ by multiple converging mechanisms leading to restoring gut integrity and homeostasis and reshaping microbiota composition.


Subject(s)
Bacillus clausii , Gastrointestinal Microbiome , Intestinal Diseases , Probiotics , Animals , Mice , Anti-Bacterial Agents/therapeutic use , Bacillus clausii/physiology , Spores, Bacterial , Intestinal Diseases/drug therapy , Intestinal Mucosa , Probiotics/pharmacology
14.
Int Immunopharmacol ; 119: 110205, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37104917

ABSTRACT

Irinotecan (CPT-11) is a topoisomerase I inhibitor that was approved for cancer treatment in 1994. To date, this natural product derivative remains the world's leading antitumor drug. However, the clinical application of irinotecan is limited due to its side effects, the most troubling of which is intestinal toxicity. In addition, irinotecan has certain toxicity to cells and even causes cellular senescence. Committed to developing alternatives to prevent these adverse reactions, we evaluated the activity of artesunate, which has never been tested in this regard despite its biological potential. Irinotecan accelerated the process of aging in vivo and in vitro, and we found that this was mainly caused by activating mTOR signaling targets. Artesunate inhibited the activity of mTOR, thereby alleviating the aging process. Our study found that artesunate treatment improved irinotecan-induced intestinal inflammation by reducing the levels of TNF-α, IL1, and IL6; reducing inflammatory infiltration of the colonic ileum in mice; and preventing irinotecan-induced intestinal damage by reducing weight loss and improving intestinal length. In addition, in mouse xenograft tumor models, artesunate and irinotecan significantly inhibited tumor growth in mice.


Subject(s)
Antineoplastic Agents , Artesunate , Intestinal Diseases , Irinotecan , Topoisomerase I Inhibitors , Artesunate/therapeutic use , Humans , Animals , Mice , Antineoplastic Agents/therapeutic use , Irinotecan/adverse effects , Intestinal Diseases/chemically induced , Intestinal Diseases/drug therapy , Cellular Senescence , Topoisomerase I Inhibitors/adverse effects
15.
Curr Atheroscler Rep ; 25(5): 181-187, 2023 05.
Article in English | MEDLINE | ID: mdl-36897412

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease. RECENT FINDINGS: Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia. Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.


Subject(s)
Atherosclerosis , Hypercholesterolemia , Hyperlipoproteinemia Type II , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Xanthomatosis , Humans , Hypercholesterolemia/drug therapy , Phytosterols/adverse effects , Phytosterols/genetics , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/therapy , Intestinal Diseases/diagnosis , Intestinal Diseases/genetics , Intestinal Diseases/drug therapy , Hyperlipoproteinemia Type II/complications , Cholesterol , Xanthomatosis/etiology , Atherosclerosis/genetics , Atherosclerosis/complications
16.
Curr Opin Endocrinol Diabetes Obes ; 30(2): 123-127, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36597814

ABSTRACT

PURPOSE OF REVIEW: The aim of this study was to assess the potential value of the measurement of plasma xenosterols (or phytosterols) concentrations in clinical practice. RECENT FINDINGS: Recent genetic studies suggest that individuals with elevated plasma phytosterol concentrations due to monogenic and polygenic variants are at an increased risk of coronary artery disease. This supports early observations that elevated plasma phytosterol concentrations are per se atherogenic. SUMMARY: Measurement of plasma phytosterols can identify individuals with xenosterolemia (or phytosterolemia). This may be clinically useful in four ways: Establishing a diagnosis and informing management of patients with homozygous phytosterolemia; Providing a comprehensive differential diagnosis for familial hypercholesterolemia; Providing an index of cholesterol absorption that may inform personalized pharmacotherapy; and Informing more precise assessment of risk of cardiovascular disease.


Subject(s)
Hypercholesterolemia , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Humans , Hypercholesterolemia/chemically induced , Hypercholesterolemia/drug therapy , Lipid Metabolism, Inborn Errors/chemically induced , Lipid Metabolism, Inborn Errors/drug therapy , Lipid Metabolism, Inborn Errors/genetics , Phytosterols/adverse effects , Intestinal Diseases/chemically induced , Intestinal Diseases/drug therapy
17.
Clin Immunol ; 247: 109241, 2023 02.
Article in English | MEDLINE | ID: mdl-36702180

ABSTRACT

OBJECTIVES: The pilot study aims to explore the efficacy and safety of baricitinib in treating refractory intestinal Behçet's disease (BD). METHODS: We consecutively enrolled patients with refractory intestinal BD from October 2020 to September 2022. They were treated with baricitinib 2-4 mg daily, with background glucocorticoids and immunosuppressants. Efficacy assessment included the global gastrointestinal symptom scores, the endoscopy scores, the Disease activity index for intestinal Behçet's disease (DAIBD), and the inflammatory parameters. Side effects were recorded. RESULTS: The thirteen patients (six males and seven females) had a median follow-up of eleven months, 76.92% (10/13) patients achieved complete remission of global gastrointestinal symptom scores, and 66.7% (6/9) had mucosal healing on endoscopy. The DAIBD scores decreased significantly, as well as the C-reactive protein level. Baricitinib showed a glucocorticoid-sparing effect, and the safety profile is favorable. CONCLUSION: Baricitinib might be a potential choice in treating refractory intestinal BD.


Subject(s)
Behcet Syndrome , Intestinal Diseases , Male , Female , Humans , Pilot Projects , Behcet Syndrome/drug therapy , Behcet Syndrome/diagnosis , Intestines , Sulfonamides/therapeutic use , Intestinal Diseases/drug therapy , Glucocorticoids/therapeutic use
18.
Yonsei Med J ; 64(2): 111-116, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36719018

ABSTRACT

PURPOSE: Behçet's disease (BD) is a chronic inflammatory immune-mediated disease involving multiorgan systems. Gastrointestinal (GI) manifestations of BD include abdominal pain, vomiting, GI bleeding, fistula formation, obstruction, and perforation that might require surgery. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) therapy has been shown to have favorable outcomes in patients with intestinal BD who are refractory to conventional therapy. This study sought to figure out the risk factors for undergoing surgery during anti-TNF-α therapy in patients with intestinal BD. MATERIALS AND METHODS: In this retrospective analysis of intestinal BD patients who were treated with anti-TNF-α, we collected the baseline patient data including comorbidities, clinical, endoscopic, and radiologic characteristics, and the Disease Activity Index for Intestinal Behçet's Disease at the time of anti-TNF-α initiation. Each potential risk factor was compared. For multivariate analysis, Cox regression was used. RESULTS: A total of 62 patients were considered eligible for analysis, and 15 of them (24.1%) underwent surgery. In univariate analysis, the presence of extraintestinal manifestation, such as joint symptoms and erythrocyte sedimentation rate (ESR), were significantly associated with surgery during therapy. In multivariate analysis, drug response within 4 weeks [hazard ratio (HR), 64.59], skin and joint manifestation (HR, 10.23 and HR, 6.22), geographic ulcer (HR, 743.97), and ESR >42.5 mm/h (HR, 9.16) were found to be factors predictive of undergoing surgery during anti-TNF-α therapy. CONCLUSION: We found five risk factors predictive of surgery in patients with intestinal BD receiving anti-TNF-α therapy, which can guide physicians in selecting appropriate patients between anti-TNF-α therapy and early surgery.


Subject(s)
Behcet Syndrome , Intestinal Diseases , Humans , Behcet Syndrome/drug therapy , Behcet Syndrome/surgery , Intestinal Diseases/drug therapy , Intestinal Diseases/complications , Necrosis/complications , Retrospective Studies , Risk Factors , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor-alpha
19.
Gut Liver ; 17(5): 777-785, 2023 09 15.
Article in English | MEDLINE | ID: mdl-36578194

ABSTRACT

Background/Aims: To date, there is no prospective study that specifically investigated the efficacy of infliximab in intestinal Behçet's disease (BD). This study evaluated the efficacy of infliximab in patients with moderate-to-severe active intestinal BD that are refractory to conventional therapies. Methods: This phase 3, interventional, open-label, single-arm study evaluated clinical outcomes of infliximab treatment in patients with moderate-to-severe intestinal BD. The coprimary endpoints were clinical response, decrease in disease activity index for intestinal BD (DAIBD) score ≥20 from weeks 0 to 8 for the induction therapy and week 32 for the maintenance therapy. Results: A total of 33 patients entered the induction therapy and were treated with infliximab 5 mg/kg intravenously at weeks 0, 2, and 6. The mean DAIBD score changed from 90.8±40.1 at week 0 to 40.3±36.4 at week 8, with a significant mean change of 50.5±36.4 (95% confidence interval, 37.5 to 63.4; p<0.001). Thirty-one (93.9%) continued to receive 5 mg/kg infliximab every 8 weeks during the maintenance therapy. The mean change in the DAIBD score after the maintenance therapy was statistically significant (61.5±38.5; 95% confidence interval, 46.0 to 77.1; p<0.001, from weeks 0 to 32). The proportion of patients who maintained a clinical response was 92.3% at week 32. No severe adverse reactions occurred during the induction and maintenance therapies. Conclusions: This study provided evidence that infliximab 5 mg/kg induction and maintenance therapies are efficacious and well-tolerated in patients with moderate-to-severe active intestinal BD. (ClinicalTrials.gov identifier: NCT02505568).


Subject(s)
Behcet Syndrome , Intestinal Diseases , Humans , Behcet Syndrome/drug therapy , Infliximab/adverse effects , Intestinal Diseases/drug therapy , Intestines , Prospective Studies , Treatment Outcome
20.
Br J Pharmacol ; 180(2): 144-160, 2023 01.
Article in English | MEDLINE | ID: mdl-36355635

ABSTRACT

Elafin and its precursor trappin-2 are known for their contribution to the physiological mucosal shield against luminal microbes. Such a contribution seems to be particularly relevant in the gut, where the exposure of host tissues to heavy loads of microbes is constant and contributes to mucosa-associated pathologies. The expression of trappin-2/elafin has been shown to be differentially regulated in diseases associated with gut inflammation. Accumulating evidence has demonstrated the protective effects of trappin-2/elafin in gut intestinal disorders associated with acute or chronic inflammation, or with gluten sensitization disorders. The protective effects of trappin-2/elafin in the gut are discussed in terms of their pleiotropic modes of action: acting as protease inhibitors, transglutaminase substrates, antimicrobial peptides or as a regulator of pro-inflammatory transcription factors. Further, the question of the therapeutic potential of trappin-2/elafin delivery at the intestinal mucosa surface is raised. Whether trappin-2/elafin mucosal delivery should be considered to ensure intestinal tissue repair is also discussed.


Subject(s)
Elafin , Intestinal Diseases , Humans , Elafin/metabolism , Protease Inhibitors , Inflammation , Intestinal Diseases/drug therapy
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