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11 pages, 1725 KiB

Open AccessArticle

Colitis-Associated Colorectal Cancer in Patients with Inflammatory Bowel Diseases in a Tertiary Referral Center: A Propensity Score Matching Analysis

by Kasper Maryńczak, Jakub Włodarczyk, Zofia Sabatowska, Adam Dziki, Łukasz Dziki and Marcin Włodarczyk

J. Clin. Med. 2022, 11(3), 866; https://doi.org/10.3390/jcm11030866 - 07 Feb 2022

Cited by 10 | Viewed by 1826

Abstract

Background: Inflammatory bowel disease (IBD) is a risk factor in developing colitis-associated colorectal cancer (CA-CRC). CA-CRC causes the death of about 15% IBD patients and the risk is 1.5–2.4 fold higher among IBD sufferers than in the general population. The dysplasia CA-CRC develops [...] Read more.

Background: Inflammatory bowel disease (IBD) is a risk factor in developing colitis-associated colorectal cancer (CA-CRC). CA-CRC causes the death of about 15% IBD patients and the risk is 1.5–2.4 fold higher among IBD sufferers than in the general population. The dysplasia CA-CRC develops in a different mechanism in comparison to sporadic colorectal cancer (CRC). This study aimed at evaluating the surgical treatment and its outcomes as well as 5-year survival rates in the CA-CRC and sporadic CRC patients. Materials and methods: This single-center, retrospective, propensity score-matched case-control study was conducted with 2204 patients operated on due to primary CRC, who were hospitalized from 2003 to 2019. The CA-CRC group consisted of 49 patients with CRC in the course of IBD. The sporadic CRC group was selected with the propensity score matching technique and comprised 98 patients with sporadic CRC who did not have clinical or histopathological features characteristic for IBD. Results: CA-CRC is characterized by a more aggressive clinical course. Surgical treatment of CA-CRC involves more palliative operations and is related with a higher risk of perioperative and postoperative complications. Further studies of CA-CRC risk factor stratification and the development of molecular markers hold promise in reducing CRC in IBD patients in the future were warranted. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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10 pages, 6220 KiB

Open AccessArticle

Immunogenicity of BNT162b2 Vaccine in Patients with Inflammatory Bowel Disease on Infliximab Combination Therapy: A Multicenter Prospective Study

by Mohammad Shehab, Mohamed Abu-Farha, Fatema Alrashed, Ahmad Alfadhli, Khazna Alotaibi, Abdullah Alsahli, Thangavel Alphonse Thanaraj, Arshad Channanath, Hamad Ali, Jehad Abubaker and Fahd Almulla

J. Clin. Med. 2021, 10(22), 5362; https://doi.org/10.3390/jcm10225362 - 18 Nov 2021

Cited by 14 | Viewed by 2661

Abstract

Background: Vaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 vaccine clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic [...] Read more.

Background: Vaccination is a promising strategy to protect vulnerable groups like inflammatory bowel disease (IBD) patients against COVID-19 and associated severe outcomes. COVID-19 vaccine clinical trials excluded IBD patients taking infliximab with azathioprine or 6-mercaptopurine (infliximab combination). Therefore, we sought to evaluate serologic responses to COVID-19 vaccination with the mRNA vaccine, BNT162b2, in patients with IBD receiving infliximab combination therapy compared with healthy participants. Method: This was a multicenter prospective study. Patients with IBD were recruited at the time of attendance at infusion center between 1 August 2021, and 15 September 2021. Our primary outcome were the concentrations of SARS-CoV-2 antibodies 4–10 weeks after vaccination with two doses of BNT162b2 vaccine in patients with IBD taking infliximab combination therapy (study group) compared with a healthy participants group (control group). Both study and control groups were matched for age, sex, and time-since-last-vaccine-dose using optimal pair-matching method. Results: In total, 116 participants were recruited in the study, 58 patients in the study group and 58 in the control group. Median (IQR) IgG concentrations were lower in the study group (99 BAU/mL (40, 177)) than the control group (139 BAU/mL (120, 188)) following vaccination (p = 0.0032). Neutralizing antibodies were also lower in the study group compared with the control group (64% (23, 94) vs. 91% (85, 94), p < 0.001). The median IgA levels in the study group were also significantly lower when compared with the control group (6 U/mL (3, 34) vs. 13 U/mL (7, 30), p = 0.0097). In the study group, the percentages of patients who achieved positive IgG, neutralizing antibody and IgA levels were 81%, 75%, and 40%, respectively. In the control group, all participants (100%) had positive IgG and neutralizing antibody levels while 62% had positive IgA levels. Conclusion: In patients with IBD receiving infliximab combination therapy, SARS-CoV2 IgG, IgA, and neutralizing antibody levels after BNT162b2 vaccination were lower compared with healthy participants. However, most patients treated with infliximab combination therapy seroconverted after two doses of the vaccine. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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12 pages, 1190 KiB

Open AccessArticle

by Anna Pękala and Rafał Filip

J. Clin. Med. 2021, 10(22), 5311; https://doi.org/10.3390/jcm10225311 - 15 Nov 2021

Cited by 1 | Viewed by 1875

Abstract

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar [...] Read more.

Background: Primary lack or secondary loss of response to therapy with infliximab is a significant problem. This study aimed to evaluate the response to treatment in patients with Crohn’s disease (CD) and ulcerative colitis (UC) achieving therapeutic and sub-therapeutic trough levels of biosimilar infliximab (CT-P13). Results: A total of 65 patients (32 with CD and 33 with UC) were recruited. The overall response rate in both CD and UC patients exceeded 80%. There were no significant differences in treatment response and CT-P13 levels for patients with CD or UC. We did not find significant differences in the percentage of patients achieving drug levels of 3 μg/mL at week 6, 10, or 12; a significant decrease was observed at week 14. Up to 55.5% of patients with CD and 64.3% of patients with UC with sub-therapeutic CT-P13 levels at week 14 primarily responded to treatment. Conclusions: Intermediate measurements of drug levels at weeks 10 and 12 did not capture any pronounced decrease in infliximab concentrations below therapeutic levels in either group, thus suggesting no clinical usefulness. A significant percentage of patients primarily responded to treatment despite sub-therapeutic drug levels after the induction phase. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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10 pages, 259 KiB

Open AccessArticle

Epstein–Barr Virus Prevalence at Diagnosis and Seroconversion during Follow-Up in Pediatric Inflammatory Bowel Disease

by Jennifer Bachmann, Giang Le Thi, Annecarin Brückner, Anna-Lena Kalteis, Tobias Schwerd, Sibylle Koletzko and Eberhard Lurz

J. Clin. Med. 2021, 10(21), 5187; https://doi.org/10.3390/jcm10215187 - 06 Nov 2021

Cited by 3 | Viewed by 2190

Abstract

Primary Epstein–Barr virus infection in pediatric patients with inflammatory bowel disease during immunomodulation with thiopurines has been associated with increased risk for malignancies or hemophagocytic lymphohistiocytosis. We determined Epstein–Barr virus (EBV) seroprevalence at inflammatory bowel disease (IBD) diagnosis and seroconversion during follow-up in [...] Read more.

Primary Epstein–Barr virus infection in pediatric patients with inflammatory bowel disease during immunomodulation with thiopurines has been associated with increased risk for malignancies or hemophagocytic lymphohistiocytosis. We determined Epstein–Barr virus (EBV) seroprevalence at inflammatory bowel disease (IBD) diagnosis and seroconversion during follow-up in a large single center cohort of children with IBD. EBV serology results and patient characteristics were retrospectively retrieved from the hospital documentation system. EBV seronegative patients at IBD diagnosis were prospectively retested. We report on IBD patients with symptomatic active EBV infection and a complicated disease course, and those diagnosed with malignancy with respect to EBV status and drug exposure. Of 402 patients, 194 (48%) had available EBV serology results at time of IBD diagnosis at a median of 12 years (IQR 9–14 years). Thereof, 102 (53%) were EBV-positive. Of 92 EBV-negative patients, 66 were retested and 17% showed a seroconversion at a mean follow-up time of 4.3 years (SD 3 years). Three children treated with azathioprine experienced acute clinically relevant EBV infection 2, 2.5, and 4 years after IBD diagnosis, two developed signs of hemophagocytic lymphohistiocytosis. Three cases of malignancy occurred in the cohort, though none seemed to be triggered by EBV. In conclusion, almost 50% of pediatric IBD patients were EBV-naïve following diagnosis and may be at increased risk to develop severe EBV infection during immunosuppressive therapy, potentially associated with complications such as hemophagocytic lymphohistiocytosis or malignancy. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

12 pages, 550 KiB

Open AccessArticle

Fecal Levels of Lactic, Succinic and Short-Chain Fatty Acids in Patients with Ulcerative Colitis and Crohn Disease: A Pilot Study

by Olga Kaczmarczyk, Agnieszka Dąbek-Drobny, Michał Woźniakiewicz, Paweł Paśko, Justyna Dobrowolska-Iwanek, Aneta Woźniakiewicz, Agnieszka Piątek-Guziewicz, Paweł Zagrodzki, Tomasz Mach and Małgorzata Zwolińska-Wcisło

J. Clin. Med. 2021, 10(20), 4701; https://doi.org/10.3390/jcm10204701 - 13 Oct 2021

Cited by 19 | Viewed by 3011

Abstract

Intestinal dysbiosis plays a crucial role in the development of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). The importance of bacterial metabolites, such as short-chain fatty acids (SCFAs), succinic and lactic acids, as well as environmental factors that [...] Read more.

Intestinal dysbiosis plays a crucial role in the development of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). The importance of bacterial metabolites, such as short-chain fatty acids (SCFAs), succinic and lactic acids, as well as environmental factors that affect their production in the course of IBD, remains unclear. The aim of this study was to evaluate a profile of organic acids in the stool of CD and UC patients with different disease activity. We assessed a correlation between used medications, patient’s diet, and SCFA levels. A total of 35 adult patients were included in the study. We did not observe significant differences in the levels of organic acids between the CD and UC groups, irrespective of disease activity, and a control group. However, propionic acid levels were higher in IBD patients who received trimebutine vs. those who did not (p = 0.031). Higher isobutyric acid levels were observed in patients treated with biological drugs compared with those without such treatment (p = 0.014). No significant correlations were found between organic acid levels and the frequency of dietary fiber consumption. Our results reveal a new link between medication use and organic acid levels in patients with IBD. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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11 pages, 698 KiB

Open AccessArticle

Incident Crohn’s Disease as a Risk Factor for Colorectal Cancer in the First 10 Years after Diagnosis: A Nationwide Population-Based Study

by Hyunil Kim, Ji Hoon Kim, Jung Kuk Lee, Dae Ryong Kang, Su Young Kim, Hyun-Soo Kim and Hee Man Kim

J. Clin. Med. 2021, 10(20), 4663; https://doi.org/10.3390/jcm10204663 - 12 Oct 2021

Cited by 1 | Viewed by 1464

Abstract

We investigated the risk of colorectal cancer (CRC) in patients with Crohn’s disease (CD) using the claims data of the Korean National Health Insurance during 2006–2015. The data of 13,739 and 40,495 individuals with and without CD, respectively, were analyzed. Hazard ratios (HRs) [...] Read more.

We investigated the risk of colorectal cancer (CRC) in patients with Crohn’s disease (CD) using the claims data of the Korean National Health Insurance during 2006–2015. The data of 13,739 and 40,495 individuals with and without CD, respectively, were analyzed. Hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression tests. CRC developed in 25 patients (0.18%) and 42 patients (0.1%) of the CD and non-CD groups, respectively. The HR of CRC in the CD group was 2.07 (95% confidence interval (CI), 1.25–3.41). The HRs of CRC among men and women were 2.02 (95% CI 1.06–3.87) and 2.10 (95% CI, 0.96–4.62), respectively. The HRs of CRC in the age groups 0–19, 20–39, 40–59, and ≥60 years were 0.07, 4.86, 2.32, and 0.66, respectively. The HR of patients with late-onset CD (≥40 years) was significantly higher than that of those with early-onset CD (<40 years). CD patients were highly likely to develop CRC. Early-onset CD patients were significantly associated with an increased risk of CRC than matched individuals without CD. However, among CD patients, late-onset CD was significantly associated with an increased risk of CRC. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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9 pages, 839 KiB

Open AccessArticle

Serum Levels of Chemerin in Patients with Inflammatory Bowel Disease as an Indicator of Anti-TNF Treatment Efficacy

by Marcin Sochal, Jakub Fichna, Agata Gabryelska, Renata Talar-Wojnarowska, Piotr Białasiewicz and Ewa Małecka-Wojciesko

J. Clin. Med. 2021, 10(19), 4615; https://doi.org/10.3390/jcm10194615 - 08 Oct 2021

Cited by 3 | Viewed by 1601

Abstract

Chemerin belongs to the adipokines—proteins secreted by white adipose tissue. It plays an important role in angiogenesis and metabolism and its levels correlate with inflammation severity in many clinical states. Circulating chemerin levels in IBD are only rarely evaluated, with inconsistent results. The [...] Read more.

Chemerin belongs to the adipokines—proteins secreted by white adipose tissue. It plays an important role in angiogenesis and metabolism and its levels correlate with inflammation severity in many clinical states. Circulating chemerin levels in IBD are only rarely evaluated, with inconsistent results. The possible impact of anti-TNF therapy treatment in IBD on chemerin levels has not been addressed. The study aim was to evaluate the serum levels of chemerin in patients with inflammatory bowel disease (IBD), depending on disease severity as well as anti-TNF treatment. Serum chemerin was measured with ELISA in 77 patients with IBD as well as in 42 healthy controls (HCs). Twenty-six participants who underwent anti-TNF therapy were re-examined after 14 weeks. Overall, IBD patients had significantly higher serum chemerin levels than HCs. In patients with IBD exacerbation, chemerin levels were significantly higher compared to the remission group. Serum chemerin levels were significantly higher in UC patients compared to CD. Chemerin correlated with the severity of CD, but not with UC. Serum levels of chemerin decreased significantly after 14 weeks of anti-TNF treatment. Chemerin correlated with the clinical severity of IBD, and its levels decreased after anti-TNF treatment, which suggests its relationship with disease activity. It may be assumed that chemerin levels may possibly be useful for anti-TNF clinical course and treatment monitoring. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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18 pages, 1835 KiB

Open AccessArticle

Following Pediatric and Adult IBD Patients through the COVID-19 Pandemic: Changes in Psychosocial Burden and Perception of Infection Risk and Harm over Time

by Leandra Koletzko, Elisabeth Klucker, Thu Giang Le Thi, Simone Breiteneicher, Raquel Rubio-Acero, Lukas Neuhaus, Reneé G. Stark, Marie Standl, Andreas Wieser, Helga Török, Sibylle Koletzko and Tobias Schwerd

J. Clin. Med. 2021, 10(18), 4124; https://doi.org/10.3390/jcm10184124 - 13 Sep 2021

Cited by 9 | Viewed by 3167

Abstract

Background: COVID-19-associated restrictions impact societies. We investigated the impact in a large cohort of inflammatory bowel disease (IBD) patients. Methods: Pediatric (pIBD) and adult patients and pIBD parents completed validated questionnaires for self-perceived stress (Perceived Stress Questionnaire, PSQ) and quality of life from [...] Read more.

Background: COVID-19-associated restrictions impact societies. We investigated the impact in a large cohort of inflammatory bowel disease (IBD) patients. Methods: Pediatric (pIBD) and adult patients and pIBD parents completed validated questionnaires for self-perceived stress (Perceived Stress Questionnaire, PSQ) and quality of life from July to October 2020 (1st survey) and March to April 2021 (2nd survey). Analyses were stratified by age groups (6–20, >20–40, >40–60, >60 years). Perceived risk of infection and harm from COVID-19 were rated on a 1–7 scale. An index for severe outcome (SIRSCO) was calculated. Multivariable logistic regression analysis was performed. Results: Of 820 invited patients, 504 (62%, 6–85 years) patients and 86 pIBD parents completed the 1st, thereof 403 (80.4%) the 2nd survey. COVID-19 restrictions resulted in cancelled doctoral appointments (26.7%), decreased physical activity, increased food intake, unintended weight gain and sleep disturbance. PSQ increased with disease activity. Elderly males rated lower compared to females or younger adults. PSQ in pIBD mothers were comparable to moderate/severe IBD adults. Infection risk and harm were perceived high in 36% and 75.4%. Multivariable logistic models revealed associations of higher perceived risk with >3 household members, job conditions and female gender, and of perceived harm with higher SIRSCO, unintended weight change, but not with gender or age. Cancelled clinic-visits were associated with both. SARS-CoV-2 antibodies prior 2nd infection wave were positive in 2/472 (0.4%). Conclusions: IBD patients report a high degree of stress and self-perceived risk of complications from COVID-19 with major differences related to gender and age. Low seroprevalence may indicate altered immune response. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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10 pages, 551 KiB

Open AccessArticle

QRISK3 Performance in the Assessment of Cardiovascular Risk in Patients with Inflammatory Bowel Disease

by Marta Carrillo-Palau, Alejandro Hernández-Camba, Laura Ramos, Milagros Vela, Laura Arranz, Noemi Hernández Alvarez-Buylla, Inmaculada Alonso-Abreu, Anjara Hernández-Pérez, Manuel Hernández-Guerra, Camilo Palazuelos, Javier Llorca, Miguel Á. González-Gay and Iván Ferraz-Amaro

J. Clin. Med. 2021, 10(18), 4102; https://doi.org/10.3390/jcm10184102 - 11 Sep 2021

Cited by 1 | Viewed by 1874

Abstract

Inflammatory bowel disease (IBD) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Since the QRESEARCH risk estimator version 3 (QRISK3) calculator was recently proposed to assess CV in the general population, our objective was to compare [...] Read more.

Inflammatory bowel disease (IBD) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Since the QRESEARCH risk estimator version 3 (QRISK3) calculator was recently proposed to assess CV in the general population, our objective was to compare the predictive ability of QRISK3 with that of a well-established European CV risk calculator, the Systematic Coronary Risk Assessment (SCORE), to identify the presence of subclinical carotid atherosclerosis in patients with IBD. In all, 186 patients with IBD and 178 controls were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied in patients and controls. SCORE (0.2 (interquartile range 0.1–0.9) vs. 0.4 (0.1–1.4), p = 0.55) and QRISK3 1.7 ((0.6–4.6) vs. 3.0 (1.0–7.8), p = 0.16) absolute values did not differ between patients and controls. QRISK3 and SCORE correlated equally with cIMT within both populations. However, SCORE correlation with cIMT was found to be significantly lower in patients with IBD when compared to controls (Spearman’s Rho 0.715 vs. 0.587, p = 0.034). Discrimination analysis of both calculators with carotid plaque was similar within both populations. Nevertheless, in patients with IBD, QRISK3 showed a trend toward a higher discrimination (QRISK3 area under the curve 0.812 (95%CI 0.748–0.875) vs. SCORE 0.790 (95%CI 0.723–0.856), p = 0.051). In conclusion, QRISK3 discrimination for subclinical atherosclerosis is optimal and equivalent to that of SCORE in IBD patients. However, our findings highlight the role of QRISK3 as an appropriate tool for the assessment of CV risk in patients with IBD. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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22 pages, 1088 KiB

Open AccessArticle

Crohn’s Disease Susceptibility and Onset Are Strongly Related to Three NOD2 Gene Haplotypes

by Marta Kaczmarek-Ryś, Szymon Tytus Hryhorowicz, Emilia Lis, Tomasz Banasiewicz, Jacek Paszkowski, Maciej Borejsza-Wysocki, Jarosław Walkowiak, Wojciech Cichy, Piotr Krokowicz, Elżbieta Czkwianianc, Andrzej Hnatyszyn, Iwona Krela-Kaźmierczak, Agnieszka Dobrowolska, Ryszard Słomski and Andrzej Pławski

J. Clin. Med. 2021, 10(17), 3777; https://doi.org/10.3390/jcm10173777 - 24 Aug 2021

Cited by 9 | Viewed by 2839

Abstract

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 [...] Read more.

The genetic background and the determinants influencing the disease form, course, and onset of inflammatory bowel disease (IBD) remain unresolved. We aimed to determine the NOD2 gene haplotypes and their relationship with IBD occurrence, clinical presentation, and onset, analyzing a cohort of 578 patients with IBD, including children, and 888 controls. Imaging or endoscopy with a histopathological confirmation was used to diagnose IBD. Genotyping was performed to assess the differences in genotypic and allelic frequencies. Linkage disequilibrium was analyzed, and associations between haplotypes and clinical data were evaluated. We emphasized the prevalence of risk alleles in all analyzed loci in patients with Crohn disease (CD). Interestingly, c.2722G>C and c.3019_3020insC alleles were also overrepresented in ulcerative colitis (UC). T-C-G-C-insC, T-C-G-T-insC, and T-T-G-T-wt haplotypes were correlated with the late-onset form of CD (OR = 23.01, 5.09, and 17.71, respectively), while T-T-G-T-wt and C-C-G-T-wt were prevalent only in CD children (OR = 29.36, and 12.93, respectively; p-value = 0.001). In conclusion, the presence of c.3019_3020insC along with c.802C>T occurred as the most fundamental contributing diplotype in late-onset CD form, while in CD children, the mutual allele in all predisposing haplotypes was the c.2798 + 158T. Identifying the unique, high-impact haplotypes supports further studies of the NOD2 gene, including haplotypic backgrounds. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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9 pages, 239 KiB

Open AccessArticle

Social Distancing during COVID-19 Pandemic among Inflammatory Bowel Disease Patients

by Michał Łodyga, Katarzyna Maciejewska, Piotr Eder, Katarzyna Waszak, Kamila Stawczyk-Eder, Agnieszka Dobrowolska, Aleksandra Kaczka, Anita Gąsiorowska, Beata Stępień-Wrochna, Małgorzata Cicha and Grażyna Rydzewska

J. Clin. Med. 2021, 10(16), 3689; https://doi.org/10.3390/jcm10163689 - 20 Aug 2021

Cited by 3 | Viewed by 1693

Abstract

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study [...] Read more.

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study included 473 patients with IBD who made 1180 hospital visits from 1 May to 30 September 2020. During each visit, the patients completed a five-step, progressive scale that was developed to assess the degree of social isolation. In parallel, other demographic data were collected and the concentrations of anti-severe acute respiratory coronavirus 2 (SARS-CoV-2) IgG and IgM+IgA antibodies were measured using the ELISA method. (3) Results: The study found a significant correlation between the degree of social distancing and the presence of anti-SARS-CoV-2 antibodies in the groups with the lowest degree of isolation (3 to 5). (4) Conclusions: Maintaining social distancing is an effective method for reducing the spread of SARS-CoV-2 virus among IBD patients. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

9 pages, 244 KiB

Open AccessArticle

The Use of Virtual Reality to Reduce Stress among Inflammatory Bowel Disease Patients Treated with Vedolizumab

by Konrad Lewandowski, Magdalena Kaniewska, Mariusz Rosołowski, Piotr Kucha and Grażyna Rydzewska

J. Clin. Med. 2021, 10(12), 2709; https://doi.org/10.3390/jcm10122709 - 19 Jun 2021

Cited by 3 | Viewed by 1638

Abstract

(1) Background: The use of virtual reality (VR) in improving patient comfort related to medical procedures in oncology patients raised the question of whether similar benefits could be obtained by patients with inflammatory bowel disease (IBD). (2) Methods: In this prospective, randomized, controlled, [...] Read more.

(1) Background: The use of virtual reality (VR) in improving patient comfort related to medical procedures in oncology patients raised the question of whether similar benefits could be obtained by patients with inflammatory bowel disease (IBD). (2) Methods: In this prospective, randomized, controlled, single-center clinical trial, a total of 90 patients with IBD treated with vedolizumab were enrolled and randomized in a 1:1 allocation to either the VR immersion group or the routine-treated group. The primary outcome was to evaluate whether VR could decrease stress and anxiety related to a medical procedure. The secondary outcome was to assess the safety of the VR. (3) Results: A statistically significant improvement in well-being and psychological comfort (p = 0.046), feeling of relaxation (p = 0.046), sense of influence on the treatment process (p < 0.001), improved perception of the way the drug works (p < 0.001), improved positive attitude while waiting for the next administration of the drug (p = 0.026), and increased motivation for treatment (p = 0.026) was noticed in the intervention group. There were no statistically significant differences in the incidence of complications in the intervention and control groups. (4) Conclusions: The use of VR had a positive effect on the reduction of stress associated with vedolizumab treatment and could improve compliance. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

11 pages, 996 KiB

Open AccessArticle

Anti-Drug Antibodies in Patients with Inflammatory Bowel Diseases Treated with Biosimilar Infliximab: A Prospective Cohort Study

by Anna Pękala, Rafał Filip and David Aebisher

J. Clin. Med. 2021, 10(12), 2653; https://doi.org/10.3390/jcm10122653 - 16 Jun 2021

Cited by 5 | Viewed by 2201

Abstract

Reports of the prevalence of antibodies to infliximab (anti-drug antibodies, ADA) are inconsistent due in part to the various assay formats used to monitor immunogenicity in the clinic and under clinical trial settings. This study aimed to determine the frequency of ADA in [...] Read more.

Reports of the prevalence of antibodies to infliximab (anti-drug antibodies, ADA) are inconsistent due in part to the various assay formats used to monitor immunogenicity in the clinic and under clinical trial settings. This study aimed to determine the frequency of ADA in patients with inflammatory bowel disease (IBD) during induction and maintenance therapy with biosimilar infliximab (CT-P13) using the ELISA (enzyme-linked immunosorbent assay) method. In this prospective single-center study, we analyzed the incidence of ADA and the relationship between the presence of ADA and the following variables: gender, type of disease, immunosuppressive therapy used, and duration of treatment. A total of 84 patients with IBD received CT-P13 and were followed up for an average of 7 months. We found ADA in 50% of the patients with undetectable levels of the drug. The percentage of persons with antibodies detected during induction treatment was 11.3% compared to 9.6% during maintenance therapy. The analysis showed no relationship between response to treatment and antibody titers (p = 0.381). The study showed a statistically significant relationship between undetectable levels of CT-P13 and the presence of ADA at week 6 of therapy (i.e., ADA were detected in all the patients with undetectable levels of CT-P13). Patients with IBD and undetectable levels of CT-P13 before administration of the third induction dose were at high risk of the presence of anti-drug antibodies as well as primary non-response. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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13 pages, 755 KiB

Open AccessArticle

Chronic Inflammation Impairs Male Fertility—A Case-Control Study in Ulcerative Colitis Patients

by Artur Wdowiak, Mariusz Gujski, Iwona Bojar, Dorota Raczkiewicz, Joanna Bartosińska, Anita Wdowiak-Filip and Rafał Filip

J. Clin. Med. 2021, 10(7), 1460; https://doi.org/10.3390/jcm10071460 - 02 Apr 2021

Cited by 12 | Viewed by 2266

Abstract

Recent evidence indicates that a systemic state of inflammation may exert a negative effect on male fertility. The aim of this study is to evaluate sperm quality parameters in male patients with ulcerative colitis (UC). Between December 2019 and December 2020 semen analyses [...] Read more.

Recent evidence indicates that a systemic state of inflammation may exert a negative effect on male fertility. The aim of this study is to evaluate sperm quality parameters in male patients with ulcerative colitis (UC). Between December 2019 and December 2020 semen analyses are performed in 50 patients with UC in clinical remission. The control group consists of 50 healthy volunteers. Total sperm count, sperm count, percentage of morphologically normal spermatozoa, viability, and progressive motility, are significantly lower in the study group than in healthy males (p < 0.001). The DNA fragmentation index (DFI) and oxidation-reduction potential (ORP) are significantly higher in the study group (28.9% and 1.55% on average, respectively) than in healthy males (14.6% and 0.79% on average, respectively). Bacteriospermia is more clearly observed in the study group (p = 0.037), and the most frequent pathogen is Enterococcus faecalis. The DFI and ORP are significantly higher in bacteria carriers, compared to males without microbial pathogens from both the study and control groups (p < 0.001). To conclude, UC patients have worse basic sperm parameters compared to their healthy counterparts. Deterioration of semen parameters, as well as an intensified DNA fragmentation could be a result of oxidative stress intensification. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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11 pages, 2077 KiB

Open AccessArticle

MicroRNAs in Colon Tissue of Pediatric Ulcerative Pancolitis Patients Allow Detection and Prognostic Stratification

by Petr Jabandziev, Tatsuhiko Kakisaka, Julia Bohosova, Tereza Pinkasova, Lumir Kunovsky, Ondrej Slaby and Ajay Goel

J. Clin. Med. 2021, 10(6), 1325; https://doi.org/10.3390/jcm10061325 - 23 Mar 2021

Cited by 7 | Viewed by 2673

Abstract

Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the [...] Read more.

Prevalence of inflammatory bowel disease has been on the rise in recent years, especially in pediatric populations. This study aimed to provide precise identification and stratification of pediatric patients with diagnosed ulcerative colitis (UC) according to the severity of their condition and the prediction for standard treatment according to the specific expression of candidate miRNAs. We enrolled consecutive, therapeutically naïve, pediatric UC patients with confirmed pancolitis. We examined formalin-fixed paraffin-embedded specimens of colonic tissue for the expression of 10 selected candidate miRNAs. We performed receiver operating characteristic curve analysis, using area under the curve and a logistic regression model to evaluate the diagnostic and predictive power of the miRNA panels. Sixty patients were included in the final analysis. As a control group, 18 children without macroscopic and microscopic signs of inflammatory bowel disease were examined. The combination of three candidate miRNAs (let-7i-5p, miR-223-3p and miR-4284) enabled accurate detection of pediatric UC patients and controls. A panel of four candidate miRNAs (miR-375-3p, miR-146a-5p, miR-223-3p and miR-200b-3p) was associated with severity of UC in pediatric patients and a combination of three miRNAs (miR-21-5p, miR-192-5p and miR-194-5p) was associated with early relapse of the disease. Nine patients out of the total were diagnosed with primary sclerosing cholangitis (PSC) simultaneously with ulcerative colitis. A panel of 6 candidate miRNAs (miR-142-3p, miR-146a-5p, miR-223-3p, let-7i-5p, miR-192-5p and miR-194-5p) identified those patients with PSC. Specific combinations of miRNAs are promising tools for potential use in precise disease identification and severity and prognostic stratification in pediatric patients with ulcerative pancolitis. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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Review

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12 pages, 276 KiB

Open AccessReview

COVID-19 Vaccination in Inflammatory Bowel Disease (IBD)

by Aleksandra Kubas and Ewa Malecka-Wojciesko

J. Clin. Med. 2022, 11(9), 2676; https://doi.org/10.3390/jcm11092676 - 09 May 2022

Cited by 10 | Viewed by 2355

Abstract

Vaccines against SARS-CoV-2 are believed to play a key role in the suppression of the COVID-19 pandemic. However, patients suffering from inflammatory bowel diseases (IBD) were excluded from SARS-CoV-2 vaccines trials. Therefore, concerns regarding vaccination efficacy and safety among those patients were raised. [...] Read more.

Vaccines against SARS-CoV-2 are believed to play a key role in the suppression of the COVID-19 pandemic. However, patients suffering from inflammatory bowel diseases (IBD) were excluded from SARS-CoV-2 vaccines trials. Therefore, concerns regarding vaccination efficacy and safety among those patients were raised. Overall, vaccination is well tolerated in the IBD population, and different gastroenterological societies recommend vaccinating patients with IBD at the earliest opportunity to do so. Nevertheless, very little is known about the safety of COVID-19 vaccines in special IBD populations such as pregnant and breastfeeding women or pediatric patients, and further research on this matter is crucial. The available data on vaccine efficacy are promising and show high seroconversion rates in IBD patients on different immune-modifying therapies. However, patients treated with high doses of systemic corticosteroids, infliximab or infliximab and immunomodulators may have a blunted response to the vaccination. The data on COVID-19 vaccination willingness among patients with IBD are conflicting. Nevertheless, vaccine effectiveness and safety are reported to be the most common reasons for hesitancy. This review examines the effectiveness and safety of COVID-19 vaccines and describes vaccination willingness and the reasons for potential hesitancy among patients with IBD. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

17 pages, 511 KiB

Open AccessReview

Efficacy, Safety and Future Perspectives of JAK Inhibitors in the IBD Treatment

by Patrycja Dudek, Adam Fabisiak, Hubert Zatorski, Ewa Malecka-Wojciesko and Renata Talar-Wojnarowska

J. Clin. Med. 2021, 10(23), 5660; https://doi.org/10.3390/jcm10235660 - 30 Nov 2021

Cited by 16 | Viewed by 3829

Abstract

Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A [...] Read more.

Although development of biologics has importantly improved the effectiveness in inducing and maintaining remission in inflammatory bowel disease (IBD), biologic therapies still have several limitations. Effective, low-cost drug therapy with good safety profile and compliance is therefore a substantial unmet medical need. A promising target for IBD treatment strategies are Janus kinase (JAK) inhibitors, which are small molecules that interact with cytokines implicated in pathogenesis of IBD. In contrast to monoclonal antibodies, which are able to block a single cytokine, JAK inhibitors have the potential to affect multiple cytokine-dependent immune pathways, which may improve the therapeutic response in some IBD patients. Tofacitinib, inhibiting signaling via different types of JAKs, has been already approved for ulcerative colitis, and several other small-molecule are still under investigation. However, one of the main concerns about using JAK inhibitors is the risk of thromboembolic events. Moreover, patients with COVID-19 appear to have an increased susceptibility for immunothrombosis. Therefore, thrombotic complications may become a serious limitation in the use of JAK inhibitors in the SARS-CoV-2 pandemic. As many questions about safety and efficacy of small molecules still remain unclear, in our review we present the current data regarding approved JAK inhibitors, as well as those in clinical development for the treatment of IBD. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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13 pages, 782 KiB

Open AccessReview

Acute Coronary Syndromes and Inflammatory Bowel Disease: The Gut–Heart Connection

by Ayman Jaaouani, Abdulrahman Ismaiel, Stefan-Lucian Popa and Dan L. Dumitrascu

J. Clin. Med. 2021, 10(20), 4710; https://doi.org/10.3390/jcm10204710 - 14 Oct 2021

Cited by 5 | Viewed by 2788

Abstract

(1) Background: Inflammatory bowel disease (IBD) induces a process of systemic inflammation, sharing common ground with acute coronary syndromes (ACS). Growing evidence points towards a possible association between IBD and an increased risk of ACS, yet the topic is still inconclusive. Therefore, we [...] Read more.

(1) Background: Inflammatory bowel disease (IBD) induces a process of systemic inflammation, sharing common ground with acute coronary syndromes (ACS). Growing evidence points towards a possible association between IBD and an increased risk of ACS, yet the topic is still inconclusive. Therefore, we conducted a systematic review aiming to clarify these gaps in the evidence. (2) Methods: We conducted a systematic search on EMBASE, Cochrane Library, and PubMed, identifying observational studies published prior to November 2020. The diagnosis of IBD was confirmed via histopathology or codes. Full articles that fulfilled our criteria were included. Quality assessment was performed using the Newcastle–Ottawa scale (NOS). (3) Results: We included twenty observational studies with a total population of ~132 million subjects. Fifteen studies reported a significant association between ACS and IBD, while the remaining five studies reported no increase in ACS risk in IBD patients. (4) Conclusions: ACS risk in IBD patients is related to hospitalizations, acute active flares, periods of active disease, and complications, with a risk reduction during remission. Interestingly, a general increase in ACS risk was reported in younger IBD patients. The role of corticosteroids and oral contraceptive pills in increasing the ACS risk of IBD patients should be investigated. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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22 pages, 1456 KiB

Open AccessReview

Emerging Comorbidities in Inflammatory Bowel Disease: Eating Disorders, Alcohol and Narcotics Misuse

by Paweł Kuźnicki and Katarzyna Neubauer

J. Clin. Med. 2021, 10(19), 4623; https://doi.org/10.3390/jcm10194623 - 08 Oct 2021

Cited by 8 | Viewed by 5360

Abstract

Inflammatory bowel disease (IBD) is a chronic and potentially devastating condition of the digestive tract which is exemplified by increasing prevalence worldwide, byzantine pathogenesis with a poorly defined role of the environmental factors, and complex clinical demonstration. As a systemic disease, IBD may [...] Read more.

Inflammatory bowel disease (IBD) is a chronic and potentially devastating condition of the digestive tract which is exemplified by increasing prevalence worldwide, byzantine pathogenesis with a poorly defined role of the environmental factors, and complex clinical demonstration. As a systemic disease, IBD may progress with a wide spectrum of extraintestinal manifestations (EMs) and comorbidities affecting different organs and systems, from anaemia, undernutrition, and cancer to those which are often neglected like anxiety and depression. Evolving IBD epidemiology and changing environment are reflected by an expanding list of IBD-related comorbidities. In contrast to the well-established role of smoking the connection between alcohol and IBD is still debatable on many levels, from pathogenesis to complications. Furthermore, little is known about narcotics use in IBD patients, even if there are obvious factors that may predispose them to narcotics as well as alcohol misuse. Last but not least, the question arises what is the prevalence of eating disorders in IBD. In our paper, we aimed to discuss the current knowledge on alcohol and drugs misuse and eating disorders as emerging extraintestinal comorbidities in IBD. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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20 pages, 333 KiB

Open AccessReview

The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease

by Magdalena Stojek, Anna Jabłońska and Krystian Adrych

J. Clin. Med. 2021, 10(18), 4055; https://doi.org/10.3390/jcm10184055 - 08 Sep 2021

Cited by 15 | Viewed by 2404

Abstract

The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management [...] Read more.

The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

11 pages, 1015 KiB

Open AccessReview

Nutritional Therapy in Pediatric Crohn’s Disease—Are We Going to Change the Guidelines?

by Malgorzata Matuszczyk and Jaroslaw Kierkus

J. Clin. Med. 2021, 10(14), 3027; https://doi.org/10.3390/jcm10143027 - 07 Jul 2021

Cited by 5 | Viewed by 2648

Abstract

In recent years, there has been a significant increase in the incidence of Crohn’s disease. Despite significant medical progress, the treatment options available today do not meet the needs of all patients. Recent reports indicate that external environmental factors, including diet, are key [...] Read more.

In recent years, there has been a significant increase in the incidence of Crohn’s disease. Despite significant medical progress, the treatment options available today do not meet the needs of all patients. Recent reports indicate that external environmental factors, including diet, are key in the pathomechanism of the disease. It was proven that the so-called Western dietary pattern is associated with an increased risk of disease. In the pediatric population, exclusive enteral nutrition is the only nutritional therapy option recommended today with proven high efficacy in inducing remission. Recent publications that indicate at least comparable efficacy and significantly better tolerability of a specialised elimination diet, the Crohn’s Disease Exclusion Diet (CDED), provide the basis for a change in recommendations. This article discusses the mechanism of action, principles of use, and scientific evidence evaluating the efficacy of CDED in the treatment of children with Crohn’s disease. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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14 pages, 840 KiB

Open AccessReview

Impact of Cigarette Smoking on the Risk of Osteoporosis in Inflammatory Bowel Diseases

by Alicja Ewa Ratajczak, Aleksandra Szymczak-Tomczak, Anna Maria Rychter, Agnieszka Zawada, Agnieszka Dobrowolska and Iwona Krela-Kaźmierczak

J. Clin. Med. 2021, 10(7), 1515; https://doi.org/10.3390/jcm10071515 - 05 Apr 2021

Cited by 9 | Viewed by 6699

Abstract

Cigarette smoking constitutes one of the most important modifiable factors of osteoporosis, as well as contributes to an early death, tumors, and numerous chronic diseases. The group with an increased risk of a lower bone mineral density are patients suffering from inflammatory bowel [...] Read more.

Cigarette smoking constitutes one of the most important modifiable factors of osteoporosis, as well as contributes to an early death, tumors, and numerous chronic diseases. The group with an increased risk of a lower bone mineral density are patients suffering from inflammatory bowel diseases. In fact, tobacco smoke, which contains more than 7000 chemical compounds, affects bone mineral density (BMD) both directly and indirectly, as it has an impact on the RANK-RANKL-OPG pathway, intestinal microbiota composition, and calcium–phosphate balance. Constant cigarette use interferes with the production of protective mucus and inhibits the repair processes in the intestinal mucus. Nicotine as well as the other compounds of the cigarette smoke are important risk factors of the inflammatory bowel disease and osteoporosis. Additionally, cigarette smoking may decrease BMD in the IBD patients. Interestingly, it affects patients with Crohn’s disease and ulcerative colitis in different ways—on the one hand it protects against ulcerative colitis, whereas on the other it increases the risk of Crohn’s disease development. Nevertheless, all patients should be encouraged to cease smoking in order to decrease the risk of developing other disorders. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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26 pages, 1823 KiB

Open AccessReview

Repeated Fecal Microbial Transplantations and Antibiotic Pre-Treatment Are Linked to Improved Clinical Response and Remission in Inflammatory Bowel Disease: A Systematic Review and Pooled Proportion Meta-Analysis

by Valentin Mocanu, Sabitha Rajaruban, Jerry Dang, Janice Y. Kung, Edward C. Deehan and Karen L. Madsen

J. Clin. Med. 2021, 10(5), 959; https://doi.org/10.3390/jcm10050959 - 01 Mar 2021

Cited by 34 | Viewed by 3040

Abstract

The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the [...] Read more.

The response of patients with inflammatory bowel disease (IBD) to fecal microbial transplantation (FMT) has been inconsistent possibly due to variable engraftment of donor microbiota. This failure to engraft has resulted in the use of several different strategies to attempt optimization of the recipient microbiota following FMT. The purpose of our study was to evaluate the effects of two distinct microbial strategies—antibiotic pre-treatment and repeated FMT dosing—on IBD outcomes. A systematic literature review was designed and implemented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A medical librarian conducted comprehensive searches in MEDLINE, Embase, Scopus, Web of Science Core Collection, and Cochrane Library on 25 November 2019 and updated on 29 January 2021. Primary outcomes of interest included comparing relapse and remission rates in patients with IBD for a single FMT dose, repeated FMT dosages, and antibiotic pre-treatment groups. Twenty-eight articles (six randomized trials, 20 cohort trials, two case series) containing 976 patients were identified. Meta-analysis revealed that both repeated FMT and antibiotic pre-treatment strategies demonstrated improvements in pooled response and remission rates. These clinical improvements were associated with increases in fecal microbiota richness and α-diversity, as well as the enrichment of several short-chain fatty acid (SCFA)-producing anaerobes including Bifidobacterium, Roseburia, Lachnospiraceae, Prevotella, Ruminococcus, and Clostridium related species. Full article

(This article belongs to the Special Issue Advances in Inflammatory Bowel Disease)

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