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      Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain

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      Nutrients
      MDPI AG

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          Abstract

          Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six weeks of chronic unpredictable stress (depression group: n = 9, Lactobacillus intervention group: n = 7). L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly reduced depressive behaviour in the forced swimming test and tail suspension test, significantly reduced anxiety behaviour in the open field test, and reduced anxiety behaviour in the marble burying test and light/dark box test. L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly increased the brain serotonin and brain-derived neurotrophic factor concentrations, and CCFM1229 significantly decreased the serum corticosterone concentration, all of which are closely associated with the relief of depressive symptoms. Furthermore, CCFM1229 and CCFM1228 were shown to regulate purine metabolism in mice, as indicated by decreases in brain xanthine oxidase activity and an increase in liver adenosine deaminase activity. Anxiety- and depression-related indicators were significantly associated with xanthine oxidase activity in the cerebral cortex. The strains CCFM1229 and CCFM1228 reduced anxiety- and depression-related behaviour in a mouse model of chronic stress-induced depression, which may be achieved by regulating the activity of brain xanthine oxidase.

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          Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.

          There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABA(Aα2) mRNA expression in the prefrontal cortex and amygdala, but increased GABA(Aα2) in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut-brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
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            Normal gut microbiota modulates brain development and behavior

            Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
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              Depression, chronic diseases, and decrements in health: results from the World Health Surveys

              Depression is an important public-health problem, and one of the leading causes of disease burden worldwide. Depression is often comorbid with other chronic diseases and can worsen their associated health outcomes. Few studies have explored the effect of depression, alone or as a comorbidity, on overall health status. The WHO World Health Survey (WHS) studied adults aged 18 years and older to obtain data for health, health-related outcomes, and their determinants. Prevalence of depression in respondents based on ICD-10 criteria was estimated. Prevalence values for four chronic physical diseases--angina, arthritis, asthma, and diabetes--were also estimated using algorithms derived via a Diagnostic Item Probability Study. Mean health scores were constructed using factor analysis and compared across different disease states and demographic variables. The relation of these disease states to mean health scores was determined through regression modelling. Observations were available for 245 404 participants from 60 countries in all regions of the world. Overall, 1-year prevalence for ICD-10 depressive episode alone was 3.2% (95% CI 3.0-3.5); for angina 4.5% (4.3-4.8); for arthritis 4.1% (3.8-4.3); for asthma 3.3% (2.9-3.6); and for diabetes 2.0% (1.8-2.2). An average of between 9.3% and 23.0% of participants with one or more chronic physical disease had comorbid depression. This result was significantly higher than the likelihood of having depression in the absence of a chronic physical disease (p<0.0001). After adjustment for socioeconomic factors and health conditions, depression had the largest effect on worsening mean health scores compared with the other chronic conditions. Consistently across countries and different demographic characteristics, respondents with depression comorbid with one or more chronic diseases had the worst health scores of all the disease states. Depression produces the greatest decrement in health compared with the chronic diseases angina, arthritis, asthma, and diabetes. The comorbid state of depression incrementally worsens health compared with depression alone, with any of the chronic diseases alone, and with any combination of chronic diseases without depression. These results indicate the urgency of addressing depression as a public-health priority to reduce disease burden and disability, and to improve the overall health of populations.
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                Author and article information

                Contributors
                Journal
                NUTRHU
                Nutrients
                Nutrients
                MDPI AG
                2072-6643
                March 2022
                March 18 2022
                : 14
                : 6
                : 1294
                Article
                10.3390/nu14061294
                8953819
                35334950
                022df162-1d1b-4264-928b-e6a13fcdaefb
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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