Treating asthma patients with probiotics: a systematic review and meta-analysis / Tratamiento de pacientes asmáticos con probióticos: revisión sistemática y metaanálisis

Objective: to evaluate the role of probiotics in the treatment of asthma patients by meta-analysis.Methods: PubMed, Embase, The Cochrane Library, Web of Science, and other databases were searched by computer, and the relevant literature on the treatment of asthma by probiotics that met the inclusion criteria was screened by manual retrieval. Meta-analysis was performed using Revman 5.4 software and the combined effect was evaluated by odds ratio (OR) or mean difference (MD) and 95 % confidence interval (CI). Results: a total of ten references were included, all of which were randomized controlled studies, and a total of 1,101 people were investigated. Fractional exhaled nitric oxide (FeNO) (MD = -7.17, 95 % CI: -12.81, -1.54), asthma symptom severity (MD = -0.07, 95 % CI: -0.10, -0.04), Childhood Asthma Control Test (CACT) (MD = 2.26, 95 % CI: 1.14, 3.39), and the number of acute episodes of asthma (OR = 0.30, 95 % CI: 0.19, 0.47) in the probiotics group were better than those in the control group. There was no significant difference in forced expiratory volume in the first second (FEV1) (MD = 0.11, 95 % CI: -0.05, 0.26) and FEV1/FVC (%) (MD = 0.32, 95 % CI: -1.48, 2.12). Conclusion: the use of probiotics in patients with asthma can improve lung inflammation and asthma symptoms, reduce the number of asthma attacks, and have no effect on lung function.(AU)

Objetivo: evaluar el papel de los probióticos en el tratamiento de pacientes con asma mediante metaanálisis.Métodos: se realizaron búsquedas informáticas en PubMed, Embase, The Cochrane Library, Web of Science y otras bases de datos, y se examinó la literatura relevante sobre el tratamiento del asma con probióticos que cumplía con los criterios de inclusión mediante recuperación manual. El metaanálisis se realizó con el software Revman 5.4 y el efecto combinado se evaluó mediante la razón de probabilidades (OR) o diferencia media (MD) y el intervalo de confianza (IC) del 95 %. Resultados: se incluyó un total de diez referencias, todas ellas estudios controlados aleatorios, y se investigó un total de 1.101 personas. El óxido nítrico exhalado (FeNO) (MD = -7,17, IC 95 %: -12,81, -1,54), la gravedad de los síntomas del asma (MD = -0,07, IC 95 %: -0,10, -0,04), la Prueba de Control del Asma (CACT-ACT) (MD = 2,26, IC 95 %: 1,14, 3,39) y el número de episodios agudos de asma (OR = 0,30, IC 95 %: 0,19, 0,47) en el grupo de probióticos fueron mejores que en el grupo de control. No hubo diferencia significativa en volumen espiratorio forzado en el primer segundo (FEV1) (DM = 0,11, IC 95 %: -0,05, 0,26) y FEV1/FVC (%) (DM = 0,32, IC 95 %: -1,48, 2,12). Conclusión: el uso de probióticos en pacientes con asma puede mejorar la inflamación pulmonar y los síntomas del asma, reducir el número de ataques de asma y no tener efecto sobre la función pulmonar.(AU)

Current Understanding of the Roles of Gut-Brain Axis in the Cognitive Deficits Caused by Perinatal Stress Exposure.

The term 'perinatal environment' refers to the period surrounding birth, which plays a crucial role in brain development. It has been suggested that dynamic communication between the neuro-immune system and gut microbiota is essential in maintaining adequate brain function. This interaction depends on the mother's status during pregnancy and/or the newborn environment. Here, we show experimental and clinical evidence that indicates that the perinatal period is a critical window in which stress-induced immune activation and altered microbiota compositions produce lasting behavioral consequences, although a clear causative relationship has not yet been established. In addition, we discuss potential early treatments for preventing the deleterious effect of perinatal stress exposure. In this sense, early environmental enrichment exposure (including exercise) and melatonin use in the perinatal period could be valuable in improving the negative consequences of early adversities. The evidence presented in this review encourages the realization of studies investigating the beneficial role of melatonin administration and environmental enrichment exposure in mitigating cognitive alteration in offspring under perinatal stress exposure. On the other hand, direct evidence of microbiota restoration as the main mechanism behind the beneficial effects of this treatment has not been fully demonstrated and should be explored in future studies.

Lactobacillus rhamnosus KBL2290 Ameliorates Gut Inflammation in a Mouse Model of Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis, a major form of inflammatory bowel disease (IBD) associated with chronic colonic inflammation, may be induced via overreactive innate and adaptive immune responses. Restoration of gut microbiota abundance and diversity is important to control the pathogenesis. Lactobacillus spp., well-known probiotics, ameliorate IBD symptoms via various mechanisms, including modulation of cytokine production, restoration of gut tight junction activity and normal mucosal thickness, and alterations in the gut microbiota. Here, we studied the effects of oral administration of Lactobacillus rhamnosus (L. rhamnosus) KBL2290 from the feces of a healthy Korean individual to mice with DSS-induced colitis. Compared to the dextran sulfate sodium (DSS) + phosphate-buffered saline control group, the DSS + L. rhamnosus KBL2290 group evidenced significant improvements in colitis symptoms, including restoration of body weight and colon length, and decreases in the disease activity and histological scores, particularly reduced levels of pro-inflammatory cytokines and an elevated level of anti-inflammatory interleukin-10. Lactobacillus rhamnosus KBL2290 modulated the levels of mRNAs encoding chemokines and markers of inflammation; increased regulatory T cell numbers; and restored tight junction activity in the mouse colon. The relative abundances of genera Akkermansia, Lactococcus, Bilophila, and Prevotella increased significantly, as did the levels of butyrate and propionate (the major short-chain fatty acids). Therefore, oral L. rhamnosus KBL2290 may be a useful novel probiotic.

La administración prolongada de probióticos podría disminuir la frecuencia de infecciones respiratorias / Prolonged administration of probiotics may decrease the frequency of respiratory infections

Los probióticos pueden reducir la cantidad de niños diagnosticados con al menos una infección respiratoria de vías superiores (IVRS) en aproximadamente un 21%; probablemente, pueden reducir el número de niños diagnosticados con al menos tres IVRS en alrededor del 38%; pueden reducir la tasa de incidencia (número de casos nuevos durante un periodo de tiempo específico) de IVRS en alrededor del 18%; probablemente, pueden reducir el número de niños que usaron antibióticos para las IVRS en aproximadamente un 22%; y es posible que no aumenten la cantidad de personas que experimentaron efectos secundarios (cualquier daño). La evidencia que muestra una disminución en el número de niños que faltan a la guardería o a la escuela debido a las IVRS agudas con probióticos es muy incierta (AU)

Probiotics can reduce the number of children diagnosed with at least one upper respiratory infection (URTI) by approximately 21%; they can probably reduce the number of children diagnosed with at least three IVRS by about 38%; they can reduce the incidence rate (number of new cases during a specified period of time) of URTIs by about 18%; they can probably reduce the number of children using antibiotics for URTIs by about 22%; and the number of people experiencing side effects (any harm) may not increase. The evidence showing a decrease in the number of children missing daycare or school due to acute URTIs with probiotics is very uncertain. (AU)

VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial.

Importance: The effect of rationally defined nonpathogenic, nontoxigenic, commensal strains of Clostridia on prevention of Clostridioides difficile infection (CDI) is unknown. Objective: To determine the efficacy of VE303, a defined bacterial consortium of 8 strains of commensal Clostridia, in adults at high risk for CDI recurrence. The primary objective was to determine the recommended VE303 dosing for a phase 3 trial. Design, Setting, and Participants: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from February 2019 to September 2021 at 27 sites in the US and Canada. The study included 79 participants aged 18 years or older who were diagnosed with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence (defined as aged ≥75 years or ≥65 years with ≥1 risk factors: creatinine clearance <60 mL/min/1.73 m2, proton pump inhibitor use, remote [>6 months earlier] CDI history). Interventions: Participants were randomly assigned to high-dose VE303 (8.0 × 109 colony-forming units [CFUs]) (n = 30), low-dose VE303 (1.6 × 109 CFUs) (n = 27), or placebo capsules (n = 22) orally once daily for 14 days. Main Outcomes and Measures: The primary efficacy end point was the proportion of participants with CDI recurrence at 8 weeks using a combined clinical and laboratory definition. The primary efficacy end point was analyzed in 3 prespecified analyses, using successively broader definitions for an on-study CDI recurrence: (1) diarrhea consistent with CDI plus a toxin-positive stool sample; (2) diarrhea consistent with CDI plus a toxin-positive, polymerase chain reaction-positive, or toxigenic culture-positive stool sample; and (3) diarrhea consistent with CDI plus laboratory confirmation or (in the absence of a stool sample) treatment with a CDI-targeted antibiotic. Results: Baseline characteristics were similar across the high-dose VE303 (n = 29; 1 additional participant excluded from efficacy analysis), low-dose VE303 (n = 27), and placebo (n = 22) groups. The participants' median age was 63.5 years (range, 24-96); 70.5% were female; and 1.3% were Asian, 1.3% Black, 2.6% Hispanic, and 96.2% White. CDI recurrence rates through week 8 (using the efficacy analysis 3 definition) were 13.8% (4/29) for high-dose VE303, 37.0% (10/27) for low-dose VE303, and 45.5% (10/22) for placebo (P = .006, high-dose VE303 vs placebo). Conclusions and Relevance: Among adults with laboratory-confirmed CDI with 1 or more prior CDI episodes in the last 6 months and those with primary CDI at high risk for recurrence, high-dose VE303 prevented recurrent CDI compared with placebo. A larger, phase 3 study is needed to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03788434.

Oral administration of the commensal Alistipes onderdonkii prolongs allograft survival.

Intestinal commensals can exert immunomodulatory effects on the host, with beneficial or detrimental consequences depending on underlying diseases. We have previously correlated longer survival of minor mismatched skin grafts in mice with the presence of an intestinal commensal bacterium, Alistipes onderdonkii. In this study, we investigated its sufficiency and mechanism of action. Oral administration of A onderdonkii strain DSM19147 but not DSM108265 was sufficient to prolong minor mismatched skin graft survival through inhibition of tumor necrosis factor production. Through metabolomic and metagenomic comparisons between DSM19147 and DSM108265, we identified candidate gene products associated with the anti-inflammatory effect of DSM19147. A onderdonkii DSM19147 can lower inflammation both at a steady state and after transplantation and may serve as an anti-inflammatory probiotic beneficial for transplant recipients.

Probiotics and non-alcoholic fatty liver disease in children and adolescents: a systematic review

Background: non-alcoholic fatty liver disease (NAFLD) in childhood is an increasing global public health issue with significant long-term consequences. NAFLD management mainly consists of lifestyle modifications, however, adjunct pharmacological therapies are currently lacking. Gut microbiota manipulation via probiotics may alter the course of pediatric NAFLD. The objective of this systematic review was to synthesize all the available literature on the use of probiotics in children and adolescents with NAFLD. Methods: PubMed, EBSCOhost, Scopus, Web of Science, and Cochrane Library were systematically searched for trials on the use of probiotics in pediatric NAFLD. A quantitative DerSimonian Laird random effects meta-analysis was performed when possible; otherwise, a narrative summary of the study outcomes was presented and discussed. A separate search was completed to include all the ongoing registered trials on probiotics use in pediatric NAFLD. Results: five randomized controlled trials met the inclusion criteria. Of these, four trials were included in the final quantitative analysis. Probiotic therapy significantly reduced the levels of alanine aminotransferase (ALT) (mean difference: -10.39 [-19.85, -0.93]), however significant heterogeneity between studies was identified (I2, 93 %). Conclusions: there is insufficient evidence to support probiotics in the treatment of pediatric NAFLD given the substantial degree of discordance amongst the available trials. Lifestyle modifications focusing on maintaining a normal BMI and regular exercise continue to be the gold standard approach to treating NAFLD in children (AU)

Use of multi-strain probiotics in linseed meal based diet for Labeo rohita fingerlings / Uso de probióticos multi-cepas na dieta à base de farinha de linhaça para alevinos de Labeo rohita

Unavailability of probiotics in fish digestive system fingerlings is unable to digest and absorb their food properly. The current research was conducted to investigate the influence of probiotics added Linseed meal based (LMB) diet on hematology and carcass composition of Labeo rohita juveniles. Hematological parameters are essential diagnostics used to estimate the health status of fish. The usage of probiotics for fish health improvement is becoming common due to the higher demand for environment-friendly culture system in water. Linseed meal was used as a test ingredient to prepare six experimental test diets by adding probiotics (0, 1, 2, 3, 4 and 5 g/kg) and 1% indigestible chromic oxide for seventy days. According to their live wet weight, five percent feed was given to fingerlings twice a day. Fish blood and carcass samples (Whole body) were taken for hematological and carcass analysis at the end of the experiment. The highest carcass composition (crude protein; 18.72%, crude fat; 8.80% and gross energy; 2.31 kcal/g) was observed in fish fed with test diet II supplemented with probiotics (2 g/kg). Moreover, maximum RBCs number (2.62× 106mm-3), WBCs (7.84×103mm-3), PCV (24.61), platelets (63.85) and hemoglobin (7.87) had also been reported in the fish fingerlings fed on 2 g/kg of probiotics supplemented diet. Results indicated that probiotics supplementation has a critical role in improvement of fingerlings' body composition and hematological indices. Present findings showed that probiotics supplementation at 2 g/kg level in linseed by-product-based diet was very useful for enhancing the overall performance of L. rohita fingerlings.

A indisponibilidade de probióticos em alevinos do sistema digestivo de peixes faz com que ele seja incapaz de digerir e absorver seus alimentos adequadamente. A presente pesquisa foi conduzida para investigar a influência de probióticos adicionados à dieta à base de farelo de linhaça (LMB) na hematologia e na composição da carcaça de juvenis de Labeo rohita. Os parâmetros hematológicos são diagnósticos essenciais usados para estimar o estado de saúde dos peixes. O uso de probióticos para a melhoria da saúde dos peixes está se tornando comum devido à maior demanda por sistemas de cultivo em água que não agridam o meio ambiente. Farinha de linhaça foi usada como ingrediente para preparar seis dietas de teste experimentais adicionando probióticos (0, 1, 2, 3, 4 e 5 g/kg) e 1% de óxido crômico indigestível por 70 dias. De acordo com seu peso úmido vivo, 5% de alimento eram dados aos alevinos duas vezes ao dia. Amostras de sangue e carcaça de peixes (corpo inteiro) foram coletadas para análise hematológica e de carcaça no final do experimento. A maior composição da carcaça (proteína bruta, 18,72%; gordura bruta, 8,80%; e energia bruta, 2,31 kcal/g) foi observada em peixes alimentados com a dieta teste II suplementada com probióticos (2 g/kg). Além disso, os números máximos de RBCs (2,62×106 mm-3), WBCs (7,84×103 mm-3), PCV (24,61), plaquetas (63,85) e hemoglobina (7,87) também foram relatados em alevinos alimentados com 2 g/kg de dieta suplementada com probióticos. Os resultados indicaram que a suplementação de probióticos tem um papel crítico na melhoria da composição corporal dos alevinos e índices hematológicos. As descobertas atuais mostraram que a suplementação de probióticos no nível de 2 g/kg em dieta à base de subproduto de linhaça foi muito útil para melhorar o desempenho geral de alevinos de L. rohita.

Impact of Biometric Patient Data, Probiotic Supplementation, and Selected Gut Microorganisms on Calprotectin, Zonulin, and sIgA Concentrations in the Stool of Adults Aged 18-74 Years.

Alterations to the intestinal barrier may be involved in the pathogenesis of various chronic diseases. The diagnosis of mucosal barrier disruption has become a new therapeutic target for disease prevention. The aim of this study was to determine whether various patient demographic and biometric data, often not included in diagnostic analyses, may affect calprotectin, zonulin, and sIgA biomarker values. Stool markers' levels in 160 samples were measured colorimetrically. The analysis of twenty key bacteria (15 genera and 5 species) was carried out on the basis of diagnostic tests, including cultures and molecular tests. The concentrations of selected markers were within reference ranges for most patients. The sIgA level was significantly lower in participants declaring probiotics supplementation (p = 0.0464). We did not observe differences in gastrointestinal discomfort in participants. We found significant differences in the sIgA level between the 29-55 years and >55 years age-related intervals groups (p = 0.0191), together with a significant decreasing trend (p = 0.0337) in age-dependent sIgA concentration. We observed complex interdependencies and relationships between their microbiota and the analyzed biomarkers. For correct clinical application, standardized values of calprotectin and sIgA should be determined, especially in elderly patients. We observed a correlation between the composition of the gut community and biomarker levels, although it requires further in-depth analysis.

Alimentación funcional para corregir desórdenes gastrointestinales asociados a trastornos del espectro autista: una revisión sistemática / Functional feeding to correct gastrointestinal disorders associated with autism spectrum disorders: a systematic review

Antecedentes: los trastornos gastrointestinales (TGI) son comorbilidades comunes en los pacientes con trastornos del espectro autista (TEA); los tratamientos con dietas libres de gluten y caseína (LGLC) o suplementos de prebióticos/probióticos podrían reducir la severidad de los TGI. Objetivo: integrar y discutir la evidencia sobre la efectividad de las terapias con dietas LGLC y suplementos de prebióticos/probióticos sobre los TGI en pacientes con TEA. Metodología: se utilizaron las guías para la publicación de revisiones sistemáticas y metaanálisis (PRISMA). Se analizaron las características de los participantes, las intervenciones dietéticas, la administración de suplementos de prebióticos/prebióticos, los efectos de las intervenciones sobre los TGI, el riesgo de sesgo de los estudios y la seguridad de los tratamientos. Resultados: se analizaron quince investigaciones; la prevalencia de los TGI entre los pacientes con TEA fue alta (58 %; rango, 27-83 %). En más del 20 % de los pacientes intervenidos con dietas LGLC o suplementos disminuyó la severidad de los TGI (principalmente estreñimiento, diarrea y dolor abdominal). Se reportaron aumentos en los conteos de bacterias benéficas y una disminución de la proporción de bacterias patógenas tras el uso de los suplementos. Sin embargo, todas estas investigaciones presentaron sesgos metodológicos importantes. Conclusiones: aunque se han encontrado reducciones en la frecuencia y severidad de algunos TGI, la efectividad de estos tratamientos aún no se ha comprobado. Dadas las diferencias metodológicas de las investigaciones, se justifica el diseño de estudios rigurosos para evaluar los efectos terapéuticos de estos tratamientos sobre la salud gastrointestinal en pacientes con TEA (AU)

Background: gastrointestinal disorders (GIDs) are common comorbidities in patients with autism spectrum disorders (ASD); treatments with gluten- and casein-free (LGLC) diets or prebiotic/probiotic supplements may reduce the severity of GIDs. Objective: to integrate and discuss the evidence on the effectiveness of LGLC diet therapies and prebiotic/probiotic supplements on GIDs in patients with ASD. Methodology: the guidelines for the publication of systematic reviews and meta-analyses (PRISMA) were used. Participant characteristics, dietary interventions, prebiotic/prebiotic supplementation, effects of interventions on GIDs, risk of bias, and safety of treatments were analyzed. Results: fifteen investigations were analyzed; the prevalence of GIDs among patients with ASD was high (58 %; range, 27-83 %). In more than 20 % of the patients managed with LGLC diets or supplements GID severity decreased (mainly constipation, diarrhea, and abdominal pain). Increases in the counts of beneficial bacteria and a decrease in the proportion of pathogenic bacteria were reported after supplement use. However, all these investigations had significant methodological biases. Conclusions: although reductions in the frequency and severity of some GIDs have been found, the effectiveness of these treatments has not been proven yet. Given the methodological differences in the investigations, the design of rigorous studies to evaluate the therapeutic effects of these treatments on gastrointestinal health in patients with ASD is warranted (AU)

[Fermented milk and probiotic foods are an important part of population diet during SARS-CoV-2 pandemic].

The problem of increasing the population antiviral immunity is of particular importance during the third year of the SARS-CoV-2 pandemic. Concomitant intestinal dysbiosis is known to play an significant role in immune cell dysfunction. Therefore, it is very important to take measures to maintain the gut microbiota using the most affordable nutritional remedies, which include fermented milk and probiotic products designed for mass population consumption and capable of enhancing their immune defence when added to the daily diet. The aim of the study was to analyze scientific evidence highlighting the role of intestinal microbiota in maintaining the macro-organism immunological balance, and to evaluate modern fermented milk and probiotic products in terms of their effect on normalising the gut microbiota and their importance in the prevention and treatment of SARS-CoV-2. Material and methods. The presented scientific and analytical review analyzed the data of electronic resources of the Global Health platform, scientific libraries eLIBRARY.RU, Cochrane Library and CyberLeninka, the search system Google Academy¼, specialized sites for scientific publications ScienceDirect and Elsevier, bibliographic databases of articles on medical sciences MEDLINE, CDC infection diseases, Embase and PubMed- NCBI. The structural-logical, analytical and axiomatic methods were used. Results. It has been shown that normal intestinal microbiota takes part in maintaining metabolism in the digestive tract, increases the body's immune reactivity and regulates the functioning of all organs and systems. The severity of dysbiotic disorders can determine susceptibility to SARS-CoV-2, the severity of this infection course, as well as the level of post-infection and post-vaccination anti-COVID-19 immunity. The high prevalence of gut dysbacteriosis indicates the need to strengthen measures of correcting dysbiotic disorders, including the inclusion of fermented and probiotic products in the daily population diet. Conclusion. Fermented milk and probiotic products, as sources of easily digestible macronutrients, essential micronutrients, biologically active substances and beneficial live microorganisms, should be included in the daily diet during the SARS-CoV-2 pandemic to increase the adaptive capacity and immunity of the population.

Correlation of SARS­CoV­2 to cancer: Carcinogenic or anticancer? (Review).

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is highly infectious and pathogenic. Among patients with severe SARS­CoV­2­caused by corona virus disease 2019 (COVID­19), those complicated with malignant tumor are vulnerable to COVID­19 due to compromised immune function caused by tumor depletion, malnutrition and anti­tumor treatment. Cancer is closely related to the risk of severe illness and mortality in patients with COVID­19. SARS­CoV­2 could promote tumor progression and stimulate metabolism switching in tumor cells to initiate tumor metabolic modes with higher productivity efficiency, such as glycolysis, for facilitating the massive replication of SARS­CoV­2. However, it has been shown that infection with SARS­CoV­2 leads to a delay in tumor progression of patients with natural killer cell (NK cell) lymphoma and Hodgkin's lymphoma, while SARS­CoV­2 elicited anti­tumor immune response may exert a potential oncolytic role in lymphoma patients. The present review briefly summarized potential carcinogenicity and oncolytic characteristics of SARS­CoV­2 as well as strategies to protect patients with cancer during the COVID­19 pandemic.

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.

Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial.

Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose-mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.

Fish oil ameliorates neuropsychiatric behaviors and gut dysbiosis by elevating selected microbiota-derived metabolites and tissue tight junctions in rats under chronic sleep deprivation.

Neuropsychiatric behaviors caused by sleep deprivation (SD) are severe public health problems in modern society worldwide. This study investigated the effect of fish oil on neuropsychiatric behaviors, barrier injury, microbiota dysbiosis, and microbiota-derived metabolites in SD rats. The rats subjected to SD had significantly elevated blood levels of corticosteroid and lipopolysaccharides and exhibited anxiety-like behavior in the open field test, depression-like behavior in the forced swim test, and cognitive impairment in the Morris water maize test. We observed that the upregulation of proinflammatory cytokines in the SD rats resulted in colonic epithelial barrier injury including a decreased number of goblet cells and increased expression of selected tight junction proteins in the gut and brain. The gut microbiome status revealed a significant decrease in the microbial diversity in the SD rats, especially in probiotics. By contrast, a fish oil-based diet reversed SD-induced behavioral changes and improved the epithelial barrier injury and dysbiosis of the microbiota in the colon. These findings could be attributable to the increase in probiotics and short-chain fatty acid (SCFAs) production, improvement in selected intestinal barrier proteins, increase in SCFA receptor expression, and decrease in blood circulation proinflammatory status due to fish oil supplementation.

The anti-inflammatory effects of Akkermansia muciniphila and its derivates in HFD/CCL4-induced murine model of liver injury.

Inflammation plays a critical role in the promotion of hepatocyte damage and liver fibrosis. In recent years the protective role of Akkermansia muciniphila, a next-generation beneficial microbe, has been suggested for metabolic and inflammatory disorders. In this study, we aimed to evaluate the effects of live and pasteurized A. muciniphila and its extra cellular vesicles (EVs) on inflammatory markers involved in liver fibrosis in a mouse model of a high-fat diet (HFD)/carbon tetrachloride (CCl4)-induced liver injury. Firstly, the responses of hepatic stellate cells (HSCs) to live and pasteurized A. muciniphila and its EVs were examined in the quiescent and LPS-activated LX-2 cells. Next, the anti-inflammatory effects of different forms of A. muciniphila were examined in the mouse model of HFD/CCl4-induced liver injury. The gene expression of various inflammatory markers was evaluated in liver, colon, and white adipose tissues. The cytokine secretion in the liver and white adipose tissues was also measured by ELISA. The results showed that administration of live and pasteurized A. muciniphila and its EVs leads to amelioration in HSCs activation. Based on data obtained from the histopathological analysis, an improvement in gut health was observed through enhancing the epithelium and mucosal layer thickness and strengthening the intestinal integrity in all treatments. Moreover, live A. muciniphila and its EVs had inhibitory effects on liver inflammation and hepatocytes damage. In addition, the tissue cytokine production and inflammatory gene expression levels revealed that live A. muciniphila and its EVs had more pronounced anti-inflammatory effects on liver and adipose tissues. Furthermore, EVs had better effects on the modulation of gene expression related to TLRs, PPARs, and immune response in the liver. In conclusion, the present results showed that oral administration of A. muciniphila and its derivatives for four weeks could enhance the intestinal integrity and anti-inflammatory responses of the colon, adipose, and liver tissues and subsequently prevent liver injury in HFD/CCL4 mice.

Opioids and Sepsis: Elucidating the Role of the Microbiome and microRNA-146.

Sepsis has recently been defined as life-threatening organ dysfunction caused by the dysregulated host response to an ongoing or suspected infection. To date, sepsis continues to be a leading cause of morbidity and mortality amongst hospitalized patients. Many risk factors contribute to development of sepsis, including pain-relieving drugs like opioids, which are frequently prescribed post-operatively. In light of the opioid crisis, understanding the interactions between opioid use and the development of sepsis has become extremely relevant, as opioid use is associated with increased risk of infection. Given that the intestinal tract is a major site of origin of sepsis-causing microbes, there has been an increasing focus on how alterations in the gut microbiome may predispose towards sepsis and mediate immune dysregulation. MicroRNAs, in particular, have emerged as key modulators of the inflammatory response during sepsis by tempering the immune response, thereby mediating the interaction between host and microbiome. In this review, we elucidate contributing roles of microRNA 146 in modulating sepsis pathogenesis and end with a discussion of therapeutic targeting of the gut microbiome in controlling immune dysregulation in sepsis.

Deep Functional Profiling of Wild Animal Microbiomes Reveals Probiotic Bacillus pumilus Strains with a Common Biosynthetic Fingerprint.

The biodiversity of microorganisms is maintained by intricate nets of interactions between competing species. Impaired functionality of human microbiomes correlates with their reduced biodiversity originating from aseptic environmental conditions and antibiotic use. Microbiomes of wild animals are free of these selective pressures. Microbiota provides a protecting shield from invasion by pathogens in the wild, outcompeting their growth in specific ecological niches. We applied ultrahigh-throughput microfluidic technologies for functional profiling of microbiomes of wild animals, including the skin beetle, Siberian lynx, common raccoon dog, and East Siberian brown bear. Single-cell screening of the most efficient killers of the common human pathogen Staphylococcus aureus resulted in repeated isolation of Bacillus pumilus strains. While isolated strains had different phenotypes, all of them displayed a similar set of biosynthetic gene clusters (BGCs) encoding antibiotic amicoumacin, siderophore bacillibactin, and putative analogs of antimicrobials including bacilysin, surfactin, desferrioxamine, and class IId cyclical bacteriocin. Amicoumacin A (Ami) was identified as a major antibacterial metabolite of these strains mediating their antagonistic activity. Genome mining indicates that Ami BGCs with this architecture subdivide into three distinct families, characteristic of the B. pumilus, B. subtilis, and Paenibacillus species. While Ami itself displays mediocre activity against the majority of Gram-negative bacteria, isolated B. pumilus strains efficiently inhibit the growth of both Gram-positive S. aureus and Gram-negative E. coli in coculture. We believe that the expanded antagonistic activity spectrum of Ami-producing B. pumilus can be attributed to the metabolomic profile predetermined by their biosynthetic fingerprint. Ultrahigh-throughput isolation of natural probiotic strains from wild animal microbiomes, as well as their metabolic reprogramming, opens up a new avenue for pathogen control and microbiome remodeling in the food industry, agriculture, and healthcare.

The role of probiotics in children with autism spectrum disorders: A study protocol for a randomised controlled trial.

BACKGROUND: Autism spectrum disorder (ASD) is a neurological and developmental condition that begins in infancy or earlier and lasts through the individual's lifetime. The aetiology and mechanisms of ASD are not yet fully understood, and current treatment comprises mainly education and rehabilitation, without significant improvement in the core symptoms. Recent studies suggest that microbiota change in children with ASD after the ingestion of probiotics may improve the balance of microbiota and thus ASD symptoms. OBJECTIVE: The objectives of this study are to evaluate the efficacy of probiotics on the symptoms of children with ASD and the possible mechanisms involved. METHODS: This is a prospective controlled trial. A total of 160 children with ASD will be stratified and allocated to placebo and probiotics groups randomised according to the severity of their ASD symptoms. The probiotics group will be given probiotics supplements orally twice a day for 3 months and the control group will be given a placebo at the same amount, in addition to the baseline therapy of education and rehabilitation. All the children will be evaluated systematically by using different scales, questionnaires before, during, and after 3 months' treatment, as well as 3 months after discontinuation. The potential impact of probiotics on immunity and inflammation, metabolism, and metagenome will also be investigated. DISCUSSION: Our previous study showed that the abundance of intestinal flora was greatly different in children with ASD, and that Bifidobacterium was associated with the severity of ASD. In the present study, we will investigate the impact of probiotics supplementation on the symptoms of Children with ASD, with the purpose of evaluating the possible therapeutic effects of additives on ASD and of providing a reference for clinical treatment. The results will help to disclose as yet unknown relationship between probiotics and ASD. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR-2000037941).

Yoghurt consumption is associated with changes in the composition of the human gut microbiome and metabolome.

BACKGROUND: Yoghurt contains live bacteria that could contribute via modulation of the gut microbiota to its reported beneficial effects such as reduced body weight gain and lower incidence of type 2 diabetes. To date, the association between yoghurt consumption and the composition of the gut microbiota is underexplored. Here we used clinical variables, metabolomics, 16S rRNA and shotgun metagenomic sequencing data collected on over 1000 predominantly female UK twins to define the link between the gut microbiota and yoghurt-associated health benefits. RESULTS: According to food frequency questionnaires (FFQ), 73% of subjects consumed yoghurt. Consumers presented a healthier diet pattern (healthy eating index: beta = 2.17 ± 0.34; P = 2.72x10-10) and improved metabolic health characterised by reduced visceral fat (beta = -28.18 ± 11.71 g; P = 0.01). According to 16S rRNA gene analyses and whole shotgun metagenomic sequencing approach consistent taxonomic variations were observed with yoghurt consumption. More specifically, we identified higher abundance of species used as yoghurt starters Streptococcus thermophilus (beta = 0.41 ± 0.051; P = 6.14x10-12) and sometimes added Bifidobacterium animalis subsp. lactis (beta = 0.30 ± 0.052; P = 1.49x10-8) in the gut of yoghurt consumers. Replication in 1103 volunteers from the LifeLines-DEEP cohort confirmed the increase of S. thermophilus among yoghurt consumers. Using food records collected the day prior to faecal sampling we showed than an increase in these two yoghurt bacteria could be transient. Metabolomics analysis revealed that B. animalis subsp. lactis was associated with 13 faecal metabolites including a 3-hydroxyoctanoic acid, known to be involved in the regulation of gut inflammation. CONCLUSIONS: Yoghurt consumption is associated with reduced visceral fat mass and changes in gut microbiome including transient increase of yoghurt-contained species (i.e. S. thermophilus and B. lactis).