Probiotic Escherichia coli Ameliorates Antibiotic-Associated Anxiety Responses in Mice.

Despite the beneficial actions of antibiotics against bacterial infections, the use of antibiotics is a crucial etiological factor influencing microbial dysbiosis-associated adverse outcomes in human health. Based on the assumption that gut microbial dysbiosis can provoke behavioral or psychological disorders, the present study evaluated anxiety-linked behavioral changes in a mouse model of streptomycin-induced dysbiosis. Measuring anxiety-like behavior using the light-dark box and elevated plus maze tests indicated that streptomycin treatment caused acute anxiety in mice. As an intervention for dysbiosis-associated distress, the probiotic strain Escherichia coli Nissle 1917 (EcN) was evaluated for its effects on streptomycin-induced behavioral changes in mice. EcN supplementation persistently ameliorated anxiety responses in mice with streptomycin-induced dysbiosis. As an outcome of anxiety, body weight changes were marginally affected by antibiotic treatment. However, mice supplemented with EcN displayed acute retardation of body weight gain, since EcN is known to reduce food intake and increase energy expenditure. Taken together, EcN treatment prominently counteracted streptomycin-induced anxiety in mice, with the metabolically beneficial retardation of body weight gain. The present model simulates psychological disorders in antibiotic users. As a promising intervention, EcN treatment can facilitate psychological relief under conditions of dysbiotic stress by blocking the pathologic gut-brain circuit.

Impact of traditional Chinese medicine treatment on chronic unpredictable mild stress-induced depression-like behaviors: intestinal microbiota and gut microbiome function.

Gut microbiota dysbiosis is a recognized contributing factor to many noncommunicable diseases, but more evidence is still needed to illustrate its causative impact on mental and brain health disorders and mechanism(s) for targeted mitigation. Traditional Chinese Medicine (TCM) has been used in the management of neuropsychiatric diseases for many years in China. In this study, a randomized, controlled trial was conducted to examine the impact of stress on gut microbiota dysbiosis and depression, and TCM in alleviating the damage using Chronic Unpredictable Mild Stress (CUMS) rats, a well-established rodent model for depression. The behaviors of rats and the profiles of the fecal microbiota were assessed by an array of behavioral tests and 16S rRNA gene sequencing, and the intestinal microbial function was assessed by shotgun sequencing-based metagenomic analysis of microbial DNA from fecal samples. Data on brain targeted metabolites by liquid chromatography-mass spectrometry (LC-MS) were also discussed. Depressive and anxiety-like behaviors and changes in the fecal microbiota profile were observed in CUMS rats, which were then significantly reversed in CUMS rats that received TCM. Specifically, TCM treatment reduced the levels of Firmicutes, and Ruminococcus, and increased the abundance of Bacteroidetes and Roseburia, reportedly being associated with relieving psychiatric disorders. Furthermore, the levels of brain metabolites perturbed by CUMS were reversed by TCM treatment, and Spearman's correlation analysis illustrated strong correlation between brain metabolites and perturbed fecal microbiota genera. Finally, the fecal microbiome of CUMS rats was characterized by alterations in amino acid metabolism and evaluation of bile acid biosynthesis, and TCM-treated rats showed elevation of cysteine and methionine metabolism. Overall, these results indicated that administration of the TCM may mitigate CUMS-induced depression-behaviors, and it is correlated with reversing CUMS-induced intestinal microbiota dysbiosis; evidence also supported related changes in brain metabolites. These findings set up the foundation to further reveal the exact causal relationship among the TCM formula, host responses, gut microbiota dysbiosis and the levels of brain metabolites, and enabled scientific interpretation of the therapeutic function of the TCM.

Mechanisms underlying the effects of n-3 polyunsaturated fatty acids on fear memory processing and their hypothetical effects on fear of cancer recurrence in cancer survivors.

The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.

Inflammation: depression fans the flames and feasts on the heat.

Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.