Analysis of Intestinal Microflora and Metabolites From Mice With DSS-Induced IBD Treated With Schistosoma Soluble Egg Antigen

Objective: This study aimed to analyze the changes in intestinal flora and metabolites in the intestinal contents of mice with inflammatory bowel disease (IBD) to preliminarily clarify the mechanism of action of Schistosoma soluble egg antigen (SEA) on IBD, thus, laying a research foundation for the subsequent treatment of IBD.Methods: A total of 40 Institute of Cancer Research (ICR) mice were divided into four groups: control, SEA 50 μg, dextran sulfate sodium salt (DSS), and SEA 50 μg + DSS. The overall state of the animals was observed continuously during modeling. The colonic length was measured after 10 days of modeling. The degree of colonic inflammation was observed by hematoxylin and eosin staining. 16srRNA and liquid chromatography–mass spectrometry sequencing techniques were used to determine the abundance of bacteria and metabolites in the intestinal contents of mice in the DSS and SEA 50 μg + DSS groups, and the differences were further analyzed.Results: After SEA intervention, the disease activity index score of mice with IBD decreased and the colon shortening was reduced. Microscopically, the lymphocyte aggregation, glandular atrophy, goblet cell disappearance, and colonic inflammation were less in the SEA 50 μg + DSS group than in the DSS group (p < 0.0001). After SEA intervention, the abundance of beneficial bacteria prevotellaceae_UCG-001 was upregulated, while the abundance of the harmful bacteria Helicobacter, Lachnoclostridium, and Enterococcus was downregulated in the intestinal tract of mice with IBD. The intestinal metabolite analysis showed that SEA intervention decreased the intestinal contents of glycerophospholipids (lysophosphatidylcholine, lysophosphatidylethanolamine, phatidylcholine, and phatidylethanolamine) and carboxylic acids (L-alloisoleucine and L-glutamate), whereas increased bile acids and their derivatives (3B,7A,12a-trihydroxy-5A-cholanoic acid and 3A,4B, 12a-trihydroxy-5b-cholanoic acid). Combined microbiota–metabolite analysis revealed a correlation between these differential microbiota and differential metabolites. At the same time, the changes in the contents of metabolites and differential metabolites in the two groups also correlated with the abundance of the gut microbiome.Conclusions: The study showed that SEA reduced DSS-induced inflammation in IBD and improved the symptoms of IBD in mice through the combined regulation of intestinal flora and intestinal metabolism. It suggested a potential possibility for the use of SEA in treating and regulating intestinal flora and metabolism in patients with IBD.

A Case Report on Korean Medical Treatment for Induced Remission of Pediatric Crohn’s Disease

Objectives: This case study examined the effectiveness of Korean medical treatment for pediatric Crohn’s disease.Methods: A 15-year-old female Korean patient with Crohn’s disease received acupuncture, electroacupuncture, herbal medicine, moxibustion, and aromatherapy treatment for 1 month in a hospital.Results: Decreases in the Pediatric Crohn’s Disease Activity Index score (from 22.5 to 7.5) and the size of two abscesses (from 39.97 mm to 33.36 mm, and from 28.14 mm to 18.71 mm) according to an abdominal CT were observed following treatment. Nausea and vomiting disappeared, stool condition improved, and weight increased (from 30 kg to 33 kg) following treatment. Nausea and vomiting disappeared, stool condition improved, and weight increased (from 30 kg to 33 kg) following treatment.Conclusion: It would be worth examining the long-term effectiveness of Korean medical treatment for pediatric Crohn’s disease.

Assessment of a novel marker of ICU strain, the ICU Activity Index, during the COVID-19 pandemic in Victoria, Australia

OBJECTIVES: To validate a real-time Intensive Care Unit (ICU) Activity Index as a marker of ICU strain from daily data available from the Critical Health Resource Information System (CHRIS), and to investigate the association between this Index and the need to transfer critically ill patients during the coronavirus disease 2019 (COVID-19) pandemic in Victoria, Australia. DESIGN: Retrospective observational cohort study. SETTING: All 45 hospitals with an ICU in Victoria, Australia. PARTICIPANTS: Patients in all Victorian ICUs and all critically ill patients transferred between Victorian hospitals from 27 June to 6 September 2020. MAIN OUTCOME MEASURE: Acute interhospital transfer of one or more critically ill patients per day from one site to an ICU in another hospital. RESULTS: 150 patients were transported over 61 days from 29 hospitals (64%). ICU Activity Index scores were higher on days when critical care transfers occurred (median, 1.0 [IQR, 0.4–1.7] v 0.6 [IQR, 0.3–1.2]; P < 0.001). Transfers were more common on days of higher ICU occupancy, higher numbers of ventilated or COVID-19 patients, and when more critical care staff were unavailable. The highest ICU Activity Index scores were observed at hospitals in north-western Melbourne, where the COVID-19 disease burden was greatest. After adjusting for confounding factors, including occupancy and lack of available ICU staff, a rising ICU Activity Index score was associated with an increased risk of a critical care transfer (odds ratio, 4.10; 95% CI, 2.34–7.18; P < 0.001). CONCLUSIONS: The ICU Activity Index appeared to be a valid marker of ICU strain during the COVID-19 pandemic. It may be useful as a real-time clinical indicator of ICU activity and predict the need for redistribution of critical ill patients.

Gut microbiota changes in inflammatory bowel diseases and ankylosing spondilytis

Background and Aims: Both inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS) can be considered chronic immune disorders sharing common etiopathogenetic mechanisms. Changes in the composition of the intestinal microbiota, which can lead to an abnormal mucosal response, could be the missing link between these two diseases. Our study evaluate the composition of intestinal microbiota and to characterize gut dysbiosis in patients with IBD and AS. Methods: We conducted a prospective case-control study that enrolled 124 patients [20 Crohn’s disease (CD), 27 ulcerative colitis (UC), 28 AS, 17 IBD + AS and 32 controls). Intestinal microbiota analysis was performed by real-time polymerase chain reaction in stool samples. Results: The total quantity of bacteria was decreased in all investigated groups compared to the control group. In studied groups, we noticed an increased percentage of Bacteroides and Escherichia coli (E.coli) and a decreased percentage of Clostridium coccoides, Clostridium leptum, and Faecalibacterium prausnitzii compared to the control group. The percentages of Bifidobacterium (p=0.010) as well as Lactobacillus group (p=0.023) were higher in the L3 form of CD patients. In the E2 form of UC, the quantity of Bacteroides was much higher compared to the E3 form (p=0.004). In AS patients, significant correlations were observed only for the Bifidobacterium species, significantly increased in the axial form compared to peripheral disease (p=0.035). Statistically significant correlations were demonstrated between the Crohn Disease Activity Index score and the total bacterial group (p=0.023, r=-0.507), respectively Bacteroides (p=0.021, r=-0.511) and between the Mayo score and Lactobacillus (p=0.001), respectively E. coli (p=0.001). In IBD + AS group, the Crohn Disease Activity Index score was inversely correlated with the total bacterial group (p=0.010) and directly correlated with Lactobacillus (p=0.047). Conclusions: Intestinal dysbiosis is associated with both IBD and AS. In the association of IBD with AS, dysbiosis is intermediate, but it is associated with the more severe articular disease. Bifidobacterium and Lactobacillus (commonly used as probiotics!) were found to be increased in the association between active IBD and active AS. Further studies are needed to understand how dysbiosis regulates the gut immune system and contributes to intestinal and articular inflammation.

Decreased serum ACE2 levels in patients with connective tissue diseases

Objective To evaluate serum concentration and activity of angiotensin-converting enzyme 2 (ACE2) in patients with connective tissue diseases (CTDs). Methods Serum samples from healthy subjects and patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), primary Sjögren’s syndrome (SS) and rheumatoid arthritis (RA) were collected. The concentration and activity of ACE2 were measured by ELISA and fluorometric method respectively, and analyzed for associations with clinical features and concurrent medications. Results Totally 66 SLE, 55 SSc, 31 SS and 31 RA patients were involved. ACE2 concentration was significantly decreased in patients with either of the four CTDs compared with healthy subjects. The concentration was not linked to special clinical features expect that it was slightly lower in patients with lupus nephritis than those without. In SLE patients, ACE2 concentration elevated with the increase of glucocorticoids, and was not associated with other treatments. Different from the concentration, ACE2 activity was increased in CTD patients. A weak correlation of ACE2 activity with SLE disease activity index score was also observed. Conclusion The clinical significance of ACE2 concentration and activity looks quite different among CTD patients. Preliminary data suggests ACE2 levels are not affected by most of the treatments.

Microbial therapeutics for acute colitis based on genetically modified Lactococcus lactis hypersecreting IL-1Ra in mice

The increased incidence of inflammatory bowel disease (IBD) in Western and rapidly Westernizing developing countries poses a global pandemic threat. The development of affordable drugs for treating IBD worldwide is thus a priority. Genetically modified lactic acid bacteria (gmLAB) as microbial therapeutics are inexpensive protein producers suitable for use as carriers of protein to the intestinal mucosa. Here, we successfully constructed gmLAB hypersecreting interleukin 1 receptor antagonist (IL-1Ra). Oral administration of these gmLAB suppressed body weight reduction and exacerbation of the disease activity index score in mice with acute colitis and decreased the number of CD4+ IL-17A+ cells in the mesenteric lymph nodes. These data suggest that the gmLAB deliver IL-1Ra to the colon, where it inhibits IL-1 signaling. We thus developed a novel IBD therapeutic that blocks IL-1 signaling using a gmLAB protein delivery system. This system could be an inexpensive oral microbial therapeutic.

The IBD-F Patient Self-Assessment Scale Accurately Depicts the Level of Fatigue and Predicts a Negative Effect on the Quality of Life of Patients With IBD in Clinical Remission

Background Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD) and may have an unfavorable impact on quality of life (QoL). The IBD-Fatigue scale (with components SCORE1 and SCORE2) is a recently developed disease-specific questionnaire. We sought to validate a Greek version of IBD-F and use it to assess the severity and characteristics of fatigue and its effect on QoL in our study population. Methods The IBD-F scale was validated and used to obtain fatigue-related data from patients with IBD attending a tertiary care hospital. Correlations with other fatigue and QoL instruments were performed. Results The Greek IBD-F showed high internal consistency and test-retest reliability (Cronbach’s alpha = 0.901/0.966 and intraclass correlation coefficient = 0.876/0.895 for SCORE1/SCORE2, respectively). A SCORE1 &gt;7.5 suggested “significant” fatigue. In a cohort of 157 patients (mean age = 35.8 y; male patients = 52.2%; patients with Crohn disease = 65.6%), both SCORE1 and SCORE2 were significantly associated with Crohn disease (odds ratio [OR] = 4.17; 95% confidence interval [CI], 2.05-8.47; b = 8.5; 95% CI, 2.8-14.1, respectively), female sex (OR = 7.27; 95% CI, 3.19-16.6; b = 15.3; 95% CI, 9-21.6), and Harvey-Bradshaw Index/Simple Clinical Colitis Activity Index score (OR = 1.22; 95% CI, 1.06-1.39; b = 1.8; 95% CI, 0.9-2.8). A SCORE1 &gt;7.5 was present in 46% of patients in remission, and 82% of patients with a baseline SCORE1 &gt;7.5 remained fatigued at serial measurements. The SCORE1 was significantly associated with impaired QoL (P &lt; 0.001). Conclusions The validated IBD-F scale is a useful and applicable instrument for use in the IBD population. A large proportion of patients have significant fatigue, which is maintained longitudinally, independent of inflammatory activity. Fatigue impairs QoL, thus necessitating interventions that may lead to its amelioration in the IBD population.

Penyakit Crohn: Laporan Kasus

Crohn’s disease is an inflammatory transmural bowel disease with unspecific clinical characteritics. It could involve all parts of the digestive system. The exact cause of this disease remains unknown. Its manifestation depends on the location of involved intestinal mucosa, however, it could also occur extra intestinal. We reported a case of Crohn’s disease in a 54-year-old male. In this patient there was defecation with blood in stool, abdominal pain, nausea, and weight loss. Diagnosis was based on history, physical examination, endoscopic examination and colonoscopy, as well as histopathological examination. Colonoscopy EGD examination and tissue biopsy were performed on this patient and revealed esophagitis EGD classification of Los Angeles grade A and erosive gastritis. The results of colonoscopy suggested Crohn’s disease, and internal and external hemorrhoids. Pathology examination showed non-specific chronic gastritis, nonspecific chronic ileitis with datia cells, nonspecific pancolitis, and specific chronic proctitis. Disease activity measured by using CDAI (Crohn Disease Activity Index) score was 170 (mild disease). Moreover, based on the Montreal classification it was classified as A3 L3 B1 and SES-CD (Simple Endoscopic Scoring System in Crohn’s Disease) with value of 0 (not active). This patient was planned to be treated with 500 mg of mesalazine three times daily.Keywords: Crohn’s disease Abstrak: Penyakit Crohn adalah bagian dari penyakit inflamasi saluran cerna dengan karakteristik klinis yang tidak jelas, transmural, dan dapat mengenai semua bagian saluran cerna. Sampai saat ini etiologinya belum diketahui pasti. Manifestasi penyakit ini bervariasi tergantung kerusakan dari lokasi mukosa intestinal yang terkena. Manifestasi ini dapat juga terjadi di luar sistem saluran cerna. Kami melaporkan suatu kasus penyakit Crohn pada seorang laki-laki berusia 54 tahun. Pada pasien ini didapatkan buang air besar disertai darah, nyeri perut, mual dan penurunan berat badan. Diagnosis ditegakkan berdasarkan anamnesis, pemeriksaan fisik, pemeriksaan endoskopi dan kolonoskopi serta pemeriksaan histopatologik. Pemeriksaan EGD-kolonoskopi dan biopsi jarring-an dengan hasil EGD esofagitis klasifikasi Los Angeles grade A dan gastritis erosiva. Hasil kolonoskopi ialah kesan suspek penyakit Crohn dengan hemoroid interna dan eksterna. Hasil histopatologi mendapatkan gastritis kronik non spesifik, ileitis kronik non spesifik dengan sel datia, pankolitis non spesifik dan proktitis kronik non spesifik. Aktivitas penyakit diukur dengan skor CDAI sebesar 170 (aktivitas ringan) dan berdasarkan klasifikasi Montreal diklasifikasikan sebagai A3 L3 B1 dan SES-CD sebesar 0 (tidak aktif). Pasien ini direncanakan untuk diterapi dengan pemberian mesalasin 500mg tiga kali sehari.Kata kunci: penyakit Crohn

Sleep disturbance as a moderator of the association between physical activity and later pain onset among American adults aged 50 and over: evidence from the Health and Retirement Study

ObjectiveTo examine whether sleep disturbance modifies the association between physical activity and incident pain.DesignProspective population-based study.SettingHealth and Retirement Study.ParticipantsAmerican adults aged ≥50 years who reported no troublesome pain in 2014 were re-assessed for pain in 2016. Of 9828 eligible baseline respondents, 8036 (82%) had complete follow-up data for adjusted analyses (weighted analysis population N=42 407 222).ExposuresPhysical activity was assessed via interview with questions about time spent in moderate and vigorous physical activity. Sleep disturbance, assessed using a modified form of the Jenkins Sleep Scale, was examined as a potential moderator.Main outcome measureTroublesome pain.ResultsIn weighted analyses, 37.9% of the 2014 baseline pain-free sample participated in moderate or vigorous physical activity once a week or less, with an overall mean Physical Activity Index Score of 9.0 (SE=0.12). 18.6% went on to report troublesome pain in 2016. Each one-point higher on the Physical Activity Index Score was associated with a reduced odds ratio (OR) of incident pain for those who endorsed sleep disturbance never/rarely (OR=0.97, 95% CI 0.94 to 0.99), but not for those who endorsed sleep disturbance sometimes (OR=0.99, 95% CI 0.97 to 1.01) or most of the time (OR=1.01, 95% CI 0.99 to 1.03). The analysis of possible interaction demonstrated that frequency of sleep disturbance moderated the physical activity and incident pain association (Wald test: p=0.02).ConclusionsThe beneficial association of physical activity on reduced likelihood of later pain was only observed in persons who endorsed low levels of sleep disturbance.