Probiotics for autism spectrum disorder: An updated systematic review and meta-analysis of effects on symptoms.

BACKGROUND: Recent researches highlighted the significant role of the gut-brain axis and gut microbiota in autism spectrum disorder (ASD), a neurobehavioral developmental disorder characterized by a variety of neuropsychiatric and gastrointestinal symptoms, suggesting that alterations in the gut microbiota may correlate with the severity of ASD symptoms. Therefore, this study was designed to conduct a comprehensive systematic review and meta-analysis of the effectiveness of probiotic interventions in ameliorating behavioral symptoms in individuals with ASD. METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A comprehensive literature search was performed across multiple databases including the Cochrane Library, PubMed, Web of Science, and Google Scholar up until June 2024. Inclusion criteria encompassed published randomized clinical trials (RCTs), focusing on probiotic interventions and evaluating outcomes related to ASD behavior symptoms. The study utilized Cochrane's Risk of Bias 2 for bias assessment and applied random effect models with inverse variance method for statistical analysis, also addressing publication bias and conducting subgroup analyses through Begg's and Egger's tests to explore the effects of various factors on the outcomes. RESULTS: Our meta-analysis, which looked at eight studies with a total of 318 samples from ASD patients aged 1.5-20 years, showed that the probiotic intervention group had significantly better behavioral symptoms compared to the control group. This was shown by a pooled standardized mean difference (SMD) of -0.38 (95% CI: 0.58 to -0.18, p < 0.01). Subgroup analyses revealed significant findings across a variety of factors: studies conducted in the European region showed a notable improvement with an SMD of -0.44 (95%CI: 0.72 to -0.15); interventions lasting longer than three months exhibited a significant improvement with an SMD of -0.43 (95%CI: 0.65 to -0.21); and studies focusing on both participants under and greater than 10 years found significant benefits with an SMDs of -0.37 and -0.40, respectively (95%CI: 0.65 to -0.09, and 95%CI: 0.69 to -0.11, respectively). Moreover, both multi-strain probiotics and single-strain interventions showed an overall significant improvement with a SMD of -0.53 (95%CI: 0.85 to -0.22) and -0.28 (95%CI: 0.54 to -0.02), respectively. Also, the analysis confirmed the low likelihood of publication bias and the robustness of these findings. CONCLUSION: Our study highlighted the significant improvement in ASD behavioral symptoms through probiotic supplementation. The need for personalized treatment approaches and further research to confirm efficacy and safety of probiotics in ASD management is emphasized.

Epidemiological Aspects and Pattern of Intoxication among Elderly in Khorasan-Razavi; Northeast of Iran.

This study aimed to assess the risk factors and clinical-epidemiological patterns of acute poisoning among elderly individuals to guide prevention strategies. The epidemiological, clinical data, manner and cause of poisoning, and outcome of the registered elder cases (≥ 60 years old) in the clinical toxicology department of Imam Reza Hospital of Mashhad University of Medical Silences (CTD-IRH-MUMS) were investigated for nine months. The sex and age distribution of the patients were compared with the general population of Khorasan-Razavi using direct standardization. Among the 3064 cases registered at the hospital, 124 elderly patients were included in the study. The majority (71.8%) were male, with a mean age of 69.47. Male gender was found to be a significant risk factor for poisoning among elderly individuals compared to the general population (OR = 2.62) (1.55-4.42) (p-value < 0.001), however, it was not significant for age. Substance dependency, particularly on opiates, was common among the patients (56.5%), with a higher prevalence in males. Substance overdose (35.4%) and suicide (23.3%) were the most common methods of poisoning, with varying frequencies between genders (p-value = 0.002). Male gender was identified as a risk factor for opiate intoxication (OR = 4.68, CI = 1.70-11.83, p-value < 0.05) but not for suicide attempts. The average hospital stay duration was similar between male and female patients. The mean length of hospital stay was 3.53 ± 4.02 days (median = 3.0, range = 0.5-26 days) and was similar in both sexes. In conclusion, male gender and opiate dependency were highlighted as key factors in the poisoning of elderly individuals. These findings emphasize the importance of addressing these factors in preventive measures.

Ascorbic Acid Supplementation Improves Adolescent Stress-induced Cognitive Impairment Through Restoration of Behavioral, Biochemical and Electrophysiological Alterations in Male Rats.

The present research study aimed to investigate the role of Ascorbic acid (AA) on synaptic plasticity, learning, and memory impairment induced by unpredicted chronic mild stress (CUMS) in adolescent male rats. Adolescent male rats were divided into: 1) vehicle, 2) CUMS, 3-5) CUMS plus various doses of AA by oral gavage (CUMS-10/100/400 mg/kg), and 6) AA400 mg/kg by oral gavage. In Morris Water Maze, the time latency decreased, while the time spent in the target quadrant increased in CUMS group treated with AA at the dose of 400 mg/kg. In passive avoidance, the latency of entering into the dark chamber decreased in CUMS group treated with AA (400 mg/kg). In biochemical test results, nitrite and MDA significantly decreased, while thiol content, SOD, and catalase activity in CUMS group that received AA400mg/kg was increased. IL-10, BDNF and Ki67 increased, while TNF-a and AChE activity were decreased in CUMS group treated with AA simultaneously. The results of our study showed that chronic stress during adolescence could cause learning and memory disorders as well as synaptic plasticity. In addition, we showed that AA can prevent this problem by reducing oxidative stress, inflammation, increasing the amount of BDNF, and neurogenesis.

Folic acid ameliorates anxiety and depressive like behavior induced by nicotine withdrawal through restoration of behavioral and biochemical alterations in adolescent male rats.

INTRODUCTION: The present study aimed to assess the efficacy of folic acid (FA) on withdrawal following nicotine (Nic) administration in adolescent male rats. METHODS: Adolescent male rats were divided into two groups: 1) vehicle and 2)Nic (Nic-2mg/kg), and were under the treatment from 21 to 42 days of age. After that, they continued the experiment without treatment and returned to a regular diet, except for one of those who received Nic. The rats were divided into four groups where they were treated with different doses of FA (5, 10, and 15 mg/kg) and bupropion (Bup) by oral gavage, and the final group included normal rats that received only FA (15mg/kg) from 42 days of age for three weeks during which withdrawal occurred. RESULTS: Results showed that adolescent Nic exposure exacerbated the behavioral indices of anxiety- and depression-like behaviors, while FA attenuated the effects of Nic withdrawal on anxiety and depression as well as Bup. In support, the biochemical results demonstrated a balance between oxidant and antioxidant mediators in addition to increase and decrease of serotonin and monoamine oxidase (MAO) activity in cortical tissue. TNF-α as an inflammatory agent was decreased, whereas IL-10 as an anti-inflammatory parameter was increased. CONCLUSION: The present findings suggest anxiety and depression caused by Nic withdrawal were attenuated by FA more likely through reduction activity of MAO, the important enzyme responsible for serotonin metabolism along with balance between oxidant/anti-oxidant and pro-inflammatory/anti-inflammatory mediators. However, various mechanisms might be involved, which requires further investigation. IMPLICATIONS: Nic withdrawal induced depression and anxiety like behavior in rats followed by neuro-oxidative damage and neuro-inflammation. Folic acid supplementation as well as bupropion improved cognitive disorders induced by Nic withdrawal by increasing neuro-inflammation, neuro-oxidative damage.