The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

In recent years, there has been an emerging interest in the possible role of the gut microbiota as a co-factor in the development of autism spectrum disorders (ASDs), as many studies have highlighted the bidirectional communication between the gut and brain (the so-called “gut-brain axis”). Accumulating evidence has shown a link between alterations in the composition of the gut microbiota and both gastrointestinal and neurobehavioural symptoms in children with ASD. The aim of this narrative review was to analyse the current knowledge about dysbiosis and gastrointestinal (GI) disorders in ASD and assess the current evidence for the role of probiotics and other non-pharmacological approaches in the treatment of children with ASD. Analysis of the literature showed that gut dysbiosis in ASD has been widely demonstrated; however, there is no single distinctive profile of the composition of the microbiota in people with ASD. Gut dysbiosis could contribute to the low-grade systemic inflammatory state reported in patients with GI comorbidities. The administration of probiotics (mostly a mixture of Bifidobacteria, Streptococci and Lactobacilli) is the most promising treatment for neurobehavioural symptoms and bowel dysfunction, but clinical trials are still limited and heterogeneous. Well-designed, randomized, placebo-controlled clinical trials are required to validate the effectiveness of probiotics in the treatment of ASD and to identify the appropriate strains, dose, and timing of treatment.

Autism Spectrum Disorders and the Gut Microbiota.

The gut-brain axis refers to the bidirectional communication between the enteric nervous system and the central nervous system. Mounting evidence supports the premise that the intestinal microbiota plays a pivotal role in its function and has led to the more common and perhaps more accurate term gut-microbiota-brain axis. Numerous studies have identified associations between an altered microbiome and neuroimmune and neuroinflammatory diseases. In most cases, it is unknown if these associations are cause or effect; notwithstanding, maintaining or restoring homeostasis of the microbiota may represent future opportunities when treating or preventing these diseases. In recent years, several studies have identified the diet as a primary contributing factor in shaping the composition of the gut microbiota and, in turn, the mucosal and systemic immune systems. In this review, we will discuss the potential opportunities and challenges with respect to modifying and shaping the microbiota through diet and nutrition in order to treat or prevent neuroimmune and neuroinflammatory disease.

Nutritional modulation of the intestinal microbiota; future opportunities for the prevention and treatment of neuroimmune and neuroinflammatory disease.

Gastrointestinal symptoms (GIS) have been reported repeatedly in people with autism spectrum disorder (ASD) and studies have reported interesting correlations between severity of behavioral and gastrointestinal symptoms. Growing evidence indicates that the gut microbiota in ASD is altered with various shifts described at different taxonomic levels, pointing to the importance of considering the gut–brain axis in treatment of these disorders. Probiotics are live beneficial bacteria that are ingested as food or customized pills. These beneficial bacteria, when added in sufficient amounts, can correct the dysbiosis. Because probiotics have shown success in treating irritable bowel syndrome (IBS), it is plausible to investigate whether they can induce alleviation of behavioral symptoms as well. Probiotics show, in some clinical studies, their potential benefits (1) in improving gastrointestinal dysfunction, (2) in correcting dysbiosis, (3) in consequently reducing the severity of ASD symptoms. This review compiles data from selected studies that investigate these benefits and the mechanisms that mediate these effects, which include the production of metabolites, hormones, and neurotransmitters and the regulation of pro-inflammatory and regulatory cytokines. Future research based on more randomized, controlled studies with a larger population size and standardized use of strains, concentration of probiotics, duration of treatments, and methods of DNA extraction is still needed in this area, which may lead to more robust results.

https://www.mdpi.com/1422-0067/21/11/4159/pdf

The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders

This review article provides information about the origins, history, evolution and current status of the Saudi healthcare system, which is currently being transformed from a publicly financed and managed welfare system to a market-oriented, employment-based, insurance-driven system. Since its inception in the 1920s, the system has provided free healthcare to all Saudi nationals at publicly owned facilities run by government-employed administrators and healthcare providers. For millions of foreign workers in the country, healthcare at privately owned for-profit facilities has been paid for either by the employer or by the individual. At the completion of the three-stage transition, everyone in the country, whether employed in the public or private sector, is expected to have insurance coverage provided by the employer. All Ministry of Health-owned hospitals will be divested to the private sector, whereas primary health centres are likely to be retained by the government. Many of the operational details of the transition are unclear at this stage and will be worked out in the coming years. This paper provides a context for these changes and highlights some of the existing issues and weaknesses. The article also points to some of the future challenges and cautions against pitfalls involved in the complete transformation of the system.

The Saudi Healthcare System: A View from the Minaret

Increasing evidence suggests that the gut microbiota plays a key role in the central nervous system (CNS), and alterations of the gut microbiota composition due to environmental factors can contribute to neurodevelopmental disorders. Animal modeling may help to identify drugs that can normalize the altered gut microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose of the present study was to investigate the therapeutic potency of probiotics such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile hamsters. Fifty young golden Syrian hamsters weighing between 60 and 70 g were enrolled in the study. The hamsters were randomly divided into five groups, each with ten hamsters. The hamsters in the control group only received phosphate-buffered saline orally. The PPA-treated group received a neurotoxic dose of 250 mg PPA/kg body weight (BW)/day for three days. The clindamycin-treated group received 30 mg clindamycin/kg BW as a single orogastric dose on the day the experiment started. The two therapeutic groups received the same doses of PPA and clindamycin followed by 0.2 g probiotic/kg BW for three weeks. Biochemical parameters related to glutamate excitotoxicity were investigated in brain homogenates from each group of hamsters. Additionally, the development of pathogenic bacteria was monitored in stool samples from all groups. The microbiology results of the present study revealed descriptive changes in the fecal microbiota and the appearance of Clostridium species in the hamsters treated with clindamycin and PPA. Additionally, the effectiveness of the probiotic in the restoration of the normal gut microbiota was demonstrated. Moreover, clindamycin and PPA were found to induce a significant depletion of Mg2+ and γ-aminobutyric acid (GABA) and a remarkable increase in the Na+/Mg2+ and glutamate/GABA ratios but non-significant changes in the absolute levels of K+, Na+ and glutamate. The bacteria overgrowth induced by PPA and clindamycin in the present study effectively showed signs of neuronal toxicity. The study indicates that probiotics can be used safely to ameliorate glutamate excitotoxicity mostly through increasing depleted GABA and Mg2+ and decreasing the excitatory neurotransmitter, glutamate.

Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in juvenile hamsters induced by orally administered propionic acid and clindamycin.

The present study investigated the therapeutic effects of probiotics on brain intoxication induced by clindamycin and propionic acid (PPA) in hamsters. Fifty golden Syrian hamsters were randomly divided into five experimental groups of ten animals each: (A) control group receiving phosphate buffered saline; (B) oral buffered PPA-treated group being administered with a neurotoxic dose of 250 mg/kg PPA during three days; (C) oral clindamycin-treated group receiving a single dose of 30 mg clindamycin/kg; and (D, E) the two therapeutic groups being administered the same doses of clindamycin and PPA followed by probiotics for three weeks at a daily dose of 0.2 g/kg. Biochemical parameters of energy metabolism and oxidative stress were examined in brain homogenates from all hamsters. The development of pathogenic bacteria was monitored on stool samples from all hamsters. Descriptive changes in fecal microbiota and overgrowth of Clostridium species in clindamycin and PPA treated hamsters were recorded. Interestingly, probiotics were shown effective to restore normal gut microbiota. Clindamycin and PPA treatments caused an elevation in lipid peroxidation and catalase activity, as oxidative stress markers, together with a reduction in GST activity and GSH level. Energy metabolism impairment was ascertained via the activation of creatine kinase and a decrease of lactate dehydrogenase. These findings suggest that bacteria overgrowth caused by PPA and clindamycin was efficient to illustrate signs of neuronal toxicity. The present study indicates that probiotic treatment can improve poor detoxification, oxidative stress, and altered gut microbiota as mechanisms implicated in the etiology of many neurological disorders.

Therapeutic effects of probiotics on neurotoxicity induced by clindamycin and propionic acid in juvenile hamsters

Background The cost of Saudi healthcare continues to rise at an alarming rate, putting the sustainability of the public healthcare system into question. Data have shown that hospital and healthcare providers’ services represent the bulk of this rising cost, which makes the calls to reform the Saudi healthcare system more focused on payment models than at any time before. Objective The aim of this paper is to review various identified payment models that can be used to contain costs and improve the quality of the care provided. Method A literature review of articles addressing the issues of cost containment and improving the quality of healthcare by reforming the current Saudi healthcare payment policy were identified through the Ovid®, Medline, and Google® Scholar search engines. Results and Conclusions Many research articles and literature reviews have identified and discussed different models of healthcare payments. Some articles have focused on one payment model, while others have discussed different payment models that have been identified. There is an urgent need to reform the current system of healthcare payments to improve the quality of healthcare and maintain funding for universal healthcare coverage in the future. Future healthcare payment reforms should consider restructuring the current healthcare system, which is largely fragmented by providing incentives to different governmental healthcare sectors, in order to transform it into a more organized and coordinated system. Thus far, there is not a single payment model that can, by itself, reduce healthcare costs and improve healthcare quality. Future healthcare reforms should use a mixture of different payment models to pay hospitals and physicians.

How can Saudi Arabia reform its public hospital payment models? A narrative review.

Purpose Cardiotoxicity is a common complication associated with anthracyclines. Little is known regarding the rate of anthracyclines-related acute and chronic cardiotoxicity and adherence to cardiac monitoring recommendations among cancer patients. Patients and methods A single-centre retrospective cohort study was conducted from 2015 to 2018 on patients with cancer, 18 years of age and older, on anthracyclines without a history of cardiovascular diseases. Data on demographic information, comorbidities, cardiovascular events, monitoring parameters, and treatment details were obtained. The primary outcome was the incidence of anthracyclines-related cardiotoxicity both acute and chronic. The secondary outcome was to determine adherence to guideline recommendations for monitoring anthracyclines-related cardiotoxicity based on the American Society of Clinical Oncology clinical practice guidelines. Analyses included descriptive statistics and logistic regression. Institutional review board approval was obtained. Results In 235 patients identified, 28.9% developed cardiotoxicity, of which 27.2% were acute, while chronic cardiotoxicity was observed in 8.9% of subjects. Patients who received optimal cardiac monitoring had a statistically significant higher odds of developing cardiotoxicities (odds ratio=2.65, confidence interval=1.32-5.33). The risk of cardiotoxicity was higher in subjects with a history of diabetes mellitus, those using daunorubicin, and concomitant filgrastim use. Adherence to guideline recommendations was only achieved in 25.1% of the population. Echocardiography was the most common monitoring method used. Conclusion In this study, there was a high incidence of anthracyclines cardiotoxicity and poor compliance with cardiac monitoring recommendations for cancer patients on anthracyclines, which underscores acute and chronic cardiotoxicity in this population.

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Cardiotoxicity and Cardiac Monitoring Among Anthracycline-Treated Cancer Patients: A Retrospective Cohort Study

The original version of this article unfortunately contained a mistake The family name of the fourth author listed in the title was incorrect, and the correct name is Nadine Moubayed, as noted in the addresses Her name is now corrected in the author group of this article

/pdf/correction-to-therapeutic-effects-of-probiotics-on-2zd1zh5kqk.pdf

Nora Al-Orf

Papers

Probiotic treatment reduces the autistic-like excitation/inhibition imbalance in juvenile hamsters induced by orally administered propionic acid and clindamycin.

Therapeutic effects of probiotics on neurotoxicity induced by clindamycin and propionic acid in juvenile hamsters

How can Saudi Arabia reform its public hospital payment models? A narrative review.

Cardiotoxicity and Cardiac Monitoring Among Anthracycline-Treated Cancer Patients: A Retrospective Cohort Study

Correction to: Therapeutic effects of probiotics on neurotoxicity induced by clindamycin and propionic acid in juvenile hamsters.