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Gut microbiota plays an important role in maintaining respiratory health while providing protection against respiratory illnesses. However, the clinical role of probiotic strains in prevention and treatment of early-onset asthma is still debated. The present study aims to systematically review the available literature on the efficacy of probiotic supplementation, either alone or in combination with other treatments, in managing children with asthma. An electronic search was conducted across multiple databases including PubMed, Web of Science, and EMBASE. The articles reported in English, regardless of year of publication, were reviewed by independent authors for inclusion assessment. Randomized controlled studies evaluating the efficacy of probiotics in children with asthma were included in the study. Of the 203 articles reviewed, 16 were selected and summarized to provide a consistent review, and of these, eight studies reported the anti-asthmatic effects of the treatment with single and multi-strain probiotics alone, seven reported the use of probiotic strains in combination with other treatments, and one was a follow-up study. While some of the studies reported are well conducted and with promising results, no cumulative significant impact was seen for probiotic supplementation on disease parameters of asthma in children. However, the available literature is not sufficient to draw any solid conclusion about the possible use of probiotics in children with asthma, and it is necessary to expand this literature by conducting more well-designed randomized clinical trials to assess the effects of probiotic strains in children with asthma or carrying a high-risk of asthma. [Display omitted] • Probiotic strains are systematically reviewed in management of childhood asthma. • Efficacy of probiotic strains in asthma remains controversial. • The use of synbiotics, or synergistic formulations of probiotics strains with acupuncture or food bioactive ingredients, resulted in more pronounced effects. • The SIAIP Task Force emphasizes standardized participant selection, defined outcomes, probiotic strain and dosage, and thorough follow-up for robust randomized trials. [ABSTRACT FROM AUTHOR]

Background & Aims Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. Methods We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino ( rad21a ). Gut tissues were collected and analyzed. Results We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1 , a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1 ; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21 , indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB , compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. Conclusions Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB . Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons. [ABSTRACT FROM AUTHOR]