In a rodent model of autism, probiotics decrease gut leakiness in relation to gene expression of GABA receptors: Emphasize how crucial the gut–brain axis

Article

作者: El-Ansary, Afaf K. ; Al-Dbass, Abeer M. ; Al-Daihan, Sooad ; Alonazi, Mona ; Bin-Khattaf, Rawan M. ; Bhat, Ramesa Shafi

Abstract:

Objective:

Rodent models may help investigations on the possible link between autism spectrum disorder and increased permeability of the gastrointestinal (GI) tract since autistic patients frequently manifested GI troubles as comorbidities.

Methods:

Forty young male western Albino rats, weighing approximately 60–70 g and aged 3–4 weeks, were used. In each of the six experimental groups, eight animals were treated as follows. The mice in the control group (I) received phosphate-buffered saline orally. For 3 days, the animals in the propionic acid (PPA)-treated groups (II and III) were given an oral neurotoxic dose of PPA (250 mg/kg body weight each day). Group II was euthanized after 3 days; however, Group III was left alive to be euthanized alongside the other groups. The animals were kept at 22 ± 1°C and allowed to access water and normal food as needed. Identical dosages of PPA were given to the rats in the three treatment groups (IV, V, and VI), and for 3 weeks, they were given the following treatments: 0.2 g/kg body weight of pure Bifidobacterium infantis, a probiotic mixture of PROTEXIN®, Somerset, UK and pure Lactobacillus bulgaricus, respectively. The six groups underwent measurements of serum zonulin and occludin as variables associated with leaky gut, glutathione, malondialdehyde, and catalase as oxidative stress-related variables, with gamma-aminobutyric acid (GABA) receptor gene expression.

Results:

This study demonstrated the potential effects of pure or mixed probiotics in lowering zonulin and occludin as markers of increased intestinal permeability, enhancing GABA receptor expression, and reducing oxidative stress as neurotoxic effects of PPA.

Conclusions:

This study demonstrates that various probiotics protect gut barrier function and could be used to alleviate increased intestinal permeability caused by oxidative stress and impaired GABA signaling as a result of PPA neurotoxicity, addressing the clinical implications of probiotic supplements.

2024-10-01·iScience

Liver abscess induced by intestinal hypervirulent Klebsiella pneumoniae through down-regulation of tryptophan-IPA-IL22 axis

Article

作者: Xu, Huizhen ; Xu, Xiuyu ; Xu, Yizheng ; You, Xiu ; Ma, Xiangsong ; Wang, Hong ; Ji, Xuelian ; Chen, Yongzheng ; Wang, Liping

Hypervirulent Klebsiella pneumoniae (hvKp) is a significant causative agent of invasive hepatic abscess syndrome in Asia, presenting substantial clinical challenges due to its intricate pathogenesis. This study revealed the crucial role of the gut microbiota in fortifying the host's defense against hvKp infection by enhancing interleukin-22 (IL-22), probably through regulating downstream antimicrobial peptides such as Reg3β. In antibiotic-treated mice, we observed that gut microbiota disruption impaired the transformation of tryptophan to indole, a key ligand for the aryl hydrocarbon receptor (AhR), consequently affecting the regulatory functions of IL-22. Our experimental findings revealed that administering rIL-22 or indole propionic acid notably diminished the translocation of hvKp from the intestine to the liver. This research not only underscores the pivotal role of the gut microbiome in modulating tryptophan metabolism and the IL-22 pathway but also highlights its critical function in preventing hvKp migration from the colon to the liver.

2023-10-01·Pharmacology, biochemistry, and behavior

The enteric metabolite, propionic acid, impairs social behavior and increases anxiety in a rodent ASD model: Examining sex differences and the influence of the estrous cycle

Article

作者: Kavaliers, Martin ; Ossenkopp, Klaus-Peter ; Benitah, Katie C

Research suggests that certain gut and dietary factors may worsen behavioral features of autism spectrum disorder (ASD). Treatment with propionic acid (PPA) has been found to create both brain and behavioral responses in rats that are characteristic of ASD in humans. A consistent male bias in human ASD prevalence has been observed, and several sex-differential genetic and hormonal factors have been suggested to contribute to this bias. The majority of PPA studies in relation to ASD focus on male subjects; research examining the effects of PPA in females is scarce. The present study includes two experiments. Experiment 1 explored sex differences in the effects of systemic administration of PPA (500 mg/kg, ip) on adult rodent social behavior and anxiety (light-dark test). Experiment 2 investigated differential effects of systemic administration of PPA (500 mg/kg) on social behavior and anxiety in relation to fluctuating estrogen and progesterone levels during the adult rodent estrous cycle. PPA treatment impaired social behavior and increased anxiety in females to the same degree in comparison to PPA-treated males. As well, females treated with PPA in their diestrus phase did not differ significantly in comparison to females administered PPA in their proestrus phase, in terms of reduced social behavior and increased anxiety.

100 项与 Propionic acidemia(妙佑医疗) 相关的药物交易

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