Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study

Background & AimsClinical studies of using probiotics for managing ulcerative colitis (UC) in Jordan are rare. Therefore, we aimed to evaluate the effect of probiotic supplementation on the clinical disease activity and biochemical parameters in patients with mild-to-moderately active UC.Methods: thirty mild-to-moderate ulcerative colitis patients were included and randomly assigned to participate in a double-blinded randomized study to receive the treatment (3×1010 of probiotic capsules [containing nine Lactobacillus and five Bifidobacterium species], or a placebo), and included in the intention-to-treat analysis. Only 24 completed the study and were included in the per-protocol analysis. Both groups were compared in terms of clinical disease activity and biochemical parameters at the beginning and the end of the study. Registered under ClinicalTrials.gov Identifier no. NCT04223479. ResultsThere was a significant induction of remission in the probiotic group presented by improvement in the partial mayo score (PMS). Probiotic group had significantly lower stool frequency (0.00 ± 0.00 vs. 1.17± 1.19), global assessment (0.42 ± 0.51 vs. 1.00 ± 0.74, p = 0.035), and total PMS score (1.33 ± 0.49 vs. 3.42 ± 1.78). In terms of mean and percent of change in post-to pre-treatment values, there was a significant reduction in C-reactive protein, and an increase in hemoglobin, hematocrit, and RBC levels in the probiotic group (p<0.05). Additionally, there was a significant reduction in the IgA level and an increase in IL-10 levels among the probiotic group compared to the placebo group (p= 0.039). ConclusionsThe use of probiotic therapy had significantly induced remission in UC patients, this was evidenced by the improvement in the Partial Mayo score. Furthermore, probiotic therapy had an appropriate effect on changes in hemoglobin, hematocrit, C-reactive protein, IgA, and IL-10 levels.This study was registered at ClinicalTrials.gov with the number NCT04223479

Does probiotic supplementation improve quality of life in mild-to-moderately active ulcerative colitis patients in Jordan? A secondary outcome of the randomized, double-blind, placebo-controlled study

Purpose: Recent findings revealed a potential effect of a probiotic in improving quality of life (QoL) in ulcerative colitis (UC). In Jordan, there is scarce data about UC patients and QoL. Methods: Twenty-four UC patients were included in the study and were randomly allocated into probiotic (3 × 1010 probiotic capsules containing nine Lactobacillus and five Bifidobacterium species) and placebo control groups (containing polysaccharide supplied in an identical bottle) 3 times daily/6 weeks. A short inflammatory bowel disease questionnaire (SIBDQ) was used to assess the change in the quality of life in both groups at the beginning and the end of the intervention; The study was completed during the COVID-19 pandemic. Results: Patients treated with probiotics showed a higher score of social (6.92 ± 0.29, p = 0.019), bowel (6.31 ± 0.46, p = 0.001), emotional (6.47 ± 0.46, p < 0.001), and total SIBDQ scores (6.54 ± 0.29, p < 0.001) compared to the placebo group (5.75 ± 1.57, 4.72 ± 1.34, 4.42 ± 1.67 and 4.96 ± 1.27; respectively). Also, the probiotic group had significantly better scores in the systemic, social, bowel, emotional, and total SIBDQ scores in terms of pre- to post-treatment (p < 0.001). Conclusions: The use of probiotic therapy containing Lactobacillus and Bifidobacterium species had significantly improved the quality of life among UC patients, this was shown by the improvement in the scores of the systemic domain, social domain, bowel domain, emotional domain, and total SIBDQ. This study is part of a registered study at ClinicalTrials.gov with the number NCT04223479

Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy

Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C>T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines)

Generation of two patient specific GABRD variants and their isogenic controls for modeling epilepsy

Developmental and epileptic encephalopathies (DEEs) are early-onset conditions that cause intractable seizures and developmental delays. Missense variants in Gamma-aminobutyric acid type A receptor (GABAAR) subunits commonly cause DEEs. Ahring et al. (2022) showed a variant in the gene that encodes the delta subunit (GABRD) is strongly associated with the gain-of-function of extrasynaptic GABAAR. Here, we report the generation of two patient-specific human induced pluripotent stem cells (hiPSC) lines with (i) a de novo variant and (ii) a maternal variant, both for the pathogenic GABRD c.872 C&gt;T, (p.T291I). The variants in the generated cell line were corrected using the CRISPR-Cas9 gene editing technique (respective isogenic control lines).</p

Generation of eight hiPSCs lines from two pathogenic variants in CACNA1A using the CRISPR-Cas9 gene editing technology

Developmental and epileptic encephalopathies (DEEs) are rare severe neurodevelopmental disorders with a cumulative incidence of 1:6.000 live births. Many epileptic conditions arise from single nucleotide variants in CACNA1A (calcium voltage-gated channel subunit alpha1 A), encoding the CaV2.1 calcium channel subunit. Human induced pluripotent stem cells (hiPSCs) are an optimal choice for modeling DEEs, as they can be differentiated in vitro into diverse neuronal subpopulations. Here, we report the generation of hiPSC lines with two pathogenic CACNA1A variants c.1767C > T, p. (Arg589Cys), referred to as R589C and c. 2139G > A, p.(Ala713Thr), referred to as A713T, previously associated with epilepsy. The variants were introduced into a hiPSC line from a healthy individual via CRISPR-Cas9 gene editing technology