Your browser does not allow saving data (e.g. private mode): bookmarks will be lost when the tab closes.
Search PubMed
Keywords, author, journal, years — results from PubMed, abstracts with Russian translation, bookmarks in your browser.
Found: 3 214
Page 249 of 322-
The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression: Protocol for a Phase 2, Double-Blind, Placebo-Controlled Study.
BACKGROUND: The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain; it is being studied because of its potential influence in mediating mood, anxiety, and other neuropsychiatric symptoms. Previous research examining the effects of gut microbiota on neuropsychiatric disorders suggests that gut repopulation treatments such as probiotics, microbe therapy, and fecal microbiota transplantation show promising results in treating symptoms of anxiety and depression. This study explores the use of an alternative gut repopulation treatment to fecal microbiota transplantation, known as Microbial Ecosystem Therapeutic (MET)-2, as an intervention against symptoms of depression. MET-2 is a daily, orally administered capsule containing 40 bacterial strains purified from a single healthy donor. OBJECTIVE: The primary aim of this study is to assess changes in mood in people with major depression that occur pre-, post-, and during the administration of MET-2. The secondary aims are to assess changes in anxiety symptoms, blood biomarker concentrations, and the level of repopulation of healthy gut bacteria as a response to treatment. METHODS: In this study, we will recruit 60 adults aged between 18 and 45 years old with major depression and randomly assign them to treatment or placebo groups. Patients in the treatment group will receive MET-2 once a day for 6 weeks, whereas patients in the placebo group will receive a matching placebo for 6 weeks. Participants will complete biweekly visits during the treatment period and a follow-up visit at 2 weeks post treatment. As a primary outcome measure, participants' mood will be assessed using the Montgomery-Asberg Depression Rating Scale. Secondary outcome measures include changes in mood, anxiety, early stress, gastrointestinal symptoms, and tolerability of MET-2 treatment using a series of clinical scales and changes in blood markers, particularly immunoglobulins (Igs; IgA, IgG, and IgM) and inflammatory markers (C-reactive protein, tumor necrosis factor-α, transforming growth factor-β, interleukin-6, and interleukin-10). Changes in the relative abundance, diversity, and level of engraftment in fecal samples will be assessed using 16S rRNA sequencing. All data will be integrated to identify biomarkers that could indicate disease state or predict improvement in depressive symptoms in response to MET-2 treatment. RESULTS: Given the association between the gut microbiome and depression, we hypothesized that participants receiving MET-2 would experience greater improvement in depressive symptoms than those receiving placebo owing to the recolonization of the gut microbiome with healthy bacteria modulating the gut-brain axis connection. CONCLUSIONS: This study is the first of its kind to evaluate the safety and efficacy of a microbial therapy such as MET-2 in comparison with placebo for major depressive disorder. We hope that this study will also reveal the potential capabilities of microbial therapies to treat other psychiatric illnesses and mood disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT04602715; https://clinicaltrials.gov/ct2/show/NCT04602715. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31439.
-
Gut Microbiome: A Potential Indicator for Differential Diagnosis of Major Depressive Disorder and General Anxiety Disorder.
Background: Major depressive disorder (MDD) and general anxiety disorder (GAD) share many common features, leading to numerous challenges in their differential diagnosis. Given the importance of the microbiota-gut-brain axis, we investigated the differences in gut microbiota between representative cases of these two diseases and sought to develop a microbiome-based approach for their differential diagnosis. Methods: We enrolled 23 patients with MDD, 21 with GAD, and 10 healthy subjects (healthy crowd, HC) in the present study. We used 16S rRNA gene-sequencing analysis to determine the microbial compositions of the gut microbiome based on Illumina Miseq and according to the standard protocol. Results: GAD showed a significant difference in microbiota richness and diversity as compared with HC. Additionally, Otu24167, Otu19140, and Otu19751 were significantly decreased in MDD relative to HC, and Otu2581 and Otu10585 were significantly increased in GAD relative to MDD. At the genus level, the abundances of Sutterella and Fusicatenibacter were significantly lower in MDD relative to HC, and the abundances of Fusicatenibacter and Christensenellaceae_R7_group were significantly lower in GAD than in HC. The abundance of Sutterella was significantly higher whereas that of Faecalibacterium was significantly lower in GAD relative to MDD. Moreover, we observed that Christensenellaceae_R7_group negatively correlated with the factor score (Limited to Hopelessness) and total score of HAMD-24 (p < 0.05), whereas Fusicatenibacter negatively correlated with FT4 (p < 0.05). Furthermore, the GAD group showed significant differences at the genus level for Faecalibacterium, which negatively correlated with PTC (p < 0.05). Conclusions: This study elucidated a unique gut-microbiome signature associated with MDD and GAD that could facilitate differential diagnosis and targeted therapy.
-
Graded replacement of corn grain with molassed sugar beet pulp modulates the fecal microbial community and hindgut fermentation profile in lactating dairy cows.
High starch lactation diets not only enhance the risk of subacute ruminal acidosis but also of hindgut acidosis, which increases the risk of dysbiosis and the depression of fiber degradation. We recently showed that replacing corn with molassed sugar beet pulp (Bp) improved fiber degradation in high-producing dairy cattle, possibly because of an improvement of rumen and hindgut conditions for microbes by Bp feeding. However, little is known about the effects of high inclusion rates of Bp on hindgut microbes and fermentation. Thus fecal grab samples were taken from 18 high-yielding Simmental cows after 28 d of feeding 3 different levels of Bp (n = 6) for bacterial 16S rRNA amplicon sequencing. In addition, the reticular pH was continuously monitored with indwelling sensors and eating and ruminating behavior was evaluated with noseband sensors. The Bp inclusion rates were 0 g/kg (i.e., no Bp inclusion as control, CON), 120 g/kg (12Bp), or 240 g/kg (24Bp) replacing corn grain and limestone on a dry matter basis. The amount of time spent eating and ruminating was unaffected by Bp level, and the daily fluctuation in the reticular pH was reduced by 25% with Bp inclusion from 0.8 in the CON diet to 0.6 in 24Bp fed animals. Also, the fecal pH tended to increase with dietary Bp inclusion. Fecal acetate production showed a quadratic tendency with the lowest concentration (58.9%) of the total short-chain fatty acid in the 12Bp treatment. Inclusion of Bp up to 24% of the diet decreased the fecal butyrate proportion by 27%. The Shannon diversity index was increased from 5.50 to 8.09 with dietary Bp inclusion indicating increased species diversity. Of the 200 most abundant operational taxonomic units, 25 were increased by dietary Bp inclusion, whereas 15 were decreased and 7 were quadratically affected. The second most abundant group was proposed taxon "CF231" of the family Paraprevotellaceae. Although it accounted for only 2.52% of the operational taxonomic units in the CON diet, it was increased by 64% with dietary Bp inclusion. The largest relative change in the abundance was found for the genus Fibrobacter that increased more than 14-fold from 0.04% (CON) to 0.66% (24Bp). In conclusion, feeding molassed sugar beet pulp as partial substitution of corn up to 240 g/kg is a viable alternative that promotes ruminal and hindgut fermentation by supporting physiological pH and bacterial diversity.
-
An Akkermansia muciniphila subtype alleviates high-fat diet-induced metabolic disorders and inhibits the neurodegenerative process in mice.
The prevalence of obesity and diabetes, and their complicating mental disorders, severely affect public health. This study aimed to investigate the long-term effects of an Akkermansia muciniphila subtype (A. muciniphilasub) on high-fat diet-induced obesity and diabetes, and to evaluate whether this subtype can alleviate their complicated mental disorders. Whole genome sequencing and short chain fatty acid production analysis in supernatant of pure culture were performed. Female adult C57BL/6 mice were fed a high-fat diet or a normal chow diet and were gavaged with A. muciniphilasub or phosphate-buffered saline daily for 10 months. Body weight, food consumption and blood glucose were measured. At the end of the treatment period, all mice were subjected to the Y-maze test, sucrose preference test, analyses of serum, fecal microbiota analysis and histological examination. This A. muciniphilasub had 278 unique genes compared to the type strain (A. muciniphila ATCC BAA-835) and produced short chain fatty acids both. A. muciniphilasub administration significantly reduced body weight gain and improved the spatial memory of high-fat diet-fed mice. A. muciniphilasub increased Nissl bodies in neurons of the hippocampus, and restored the high-fat diet-inhibited tryptophan metabolism. The high-fat diet led to decreased serum 5-hydroxytryptamine and induced depression, which were not alleviated by A. muciniphilasub. A. muciniphilasub increased the relative fecal abundance of Bifidobacterium, and was negatively correlated with the fecal abundance of Bacteroides. The present study demonstrated the beneficial effects of this A. muciniphilasub on body weight, blood glucose control and the alleviation of the memory decay caused by a high-fat diet in mice.
-
Neuroinflammation: A Modifiable Pathway Linking Obesity, Alzheimer's disease, and Depression.
Obesity, depression and Alzheimer's disease (AD) are three major interrelated modern health conditions with complex relationships. Early-life depression may serve as a risk factor for AD, while late-life depression may be a prodrome of AD. Depression affects approximately 23% of obese individuals, and depression itself raises the risk of obesity by 37%. Mid-life obesity independently increases AD risk, while late-life obesity, particularly metabolically healthy obesity, may offer protection against AD pathology. Chronic inflammation serves as a key mechanism linking obesity, AD, and depression, encompassing systemic inflammation from metabolic disturbances, immune dysregulation through the gut microbiome, and direct interactions with amyloid pathology and neuroinflammation. In this review, we explore the biological mechanisms of neuroinflammation in relation to obesity, AD, and depression. We assess the efficacy of therapeutic interventions targeting neuroinflammation and discuss current and future radiological imaging initiatives for studying neuroinflammation. By comprehending the intricate interplay among depression, obesity, and AD, especially the role of neuroinflammation, we can advance our understanding and develop innovative strategies for prevention and treatment.
-
Milk fat response and milk fat and urine biomarkers of microbial nitrogen flow during supplementation with 2-hydroxy-4-(methylthio)butanoate.
2-Hydroxy-4-(methylthio)butanoate (HMTBa) is a methionine analog that has been observed to attenuate biohydrogenation (BH)-induced milk fat depression (MFD), possibly through reducing the shift to altered BH pathways. It has also been suggested that HMTBa increases microbial protein synthesis in the rumen. Our objectives were to stimulate BH-induced MFD and (1) verify HMTBa inhibition of BH-induced MFD and changes in milk fatty acids (FA) associated with altered rumen BH (i.e., trans-10 C18:1); and (2) determine the effect of HMTBa on milk fat (i.e., odd- and branched-chain FA) and urine biomarkers related to microbial N flow. Twenty-four multiparous cows (45.6 ± 8.5 kg of milk/d; mean ± standard deviation) and 12 primiparous cows (32.8 ± 3.1 kg of milk/d) were arranged in a crossover design. Treatments were unsupplemented control and HMTBa fed at 0.1% of diet dry matter intake. The experiment was 80 d and included a 10-d pretrial covariate period. Each experimental period included 2 phases that differed in risk for BH-induced MFD, including a 28-d low-risk phase (31.6% neutral detergent fiber, 21.8% starch, and no oil) and a 7-d moderate-risk phase (28.7% neutral detergent fiber, 28.1% starch, and 1.0% soybean oil). We found no interaction of treatment and parity. Milk fat yield (1.43 ± 0.51 kg/d) and milk fat trans-10 C18:1 (0.42 ± 0.08 g/100 g of FA) did not differ between treatments during the low-risk phase. However, during the moderate-risk phase, HMTBa maintained higher milk fat concentration (3.91 vs. 3.79%), tended to maintain higher milk fat yield (1.44 vs. 1.38 kg/d), and decreased milk fat trans-10 C18:1 (0.61 vs. 0.93% FA) compared with control. Additionally, HMTBa increased milk fat concentration and secretion of odd- and branched-chain FA by 5.3 and 10.2%, respectively, but urinary biomarkers of microbial N flow (i.e., purine derivatives) did not differ between treatments. However, rumen bacterial samples were not available to provide cow- or treatment-specific microbial protein-to-marker ratios, which is a critical source of variation. Additionally, transfer of odd- and branched-chain FA to milk is dependent on several factors that may affect interpretation of these biomarkers. In conclusion, HMTBa decreased absorption of alternate BH intermediates and maintained higher milk fat when feeding a diet with moderate-risk for MFD.
-
The Complex Molecular Picture of Gut and Oral Microbiota-Brain-Depression System: What We Know and What We Need to Know.
Major depressive disorder (MDD) is a complex mental disorder where the neurochemical, neuroendocrine, immune, and metabolic systems are impaired. The microbiota-gut-brain axis is a bidirectional network where the central and enteric nervous systems are linked through the same endocrine, immune, neural, and metabolic routes dysregulated in MDD. Thus, gut-brain axis abnormalities in MDD patients may, at least in part, account for the symptomatic features associated with MDD. Recent investigations have suggested that the oral microbiome also plays a key role in this complex molecular picture of relationships. As on one hand there is a lot of what we know and on the other hand little of what we still need to know, we structured this review focusing, in the first place, on putting all pieces of this complex puzzle together, underlying the endocrine, immune, oxidative stress, neural, microbial neurotransmitters, and metabolites molecular interactions and systems lying at the base of gut microbiota (GM)-brain-depression interphase. Then, we focused on promising but still under-explored areas of research strictly linked to the GM and potentially involved in MDD development: (i) the interconnection of GM with oral microbiome that can influence the neuroinflammation-related processes and (ii) gut phageome (bacteria-infecting viruses). As conclusions and future directions, we discussed potentiality but also pitfalls, roadblocks, and the gaps to be bridged in this exciting field of research. By the development of a broader knowledge of the biology associated with MDD, with the inclusion of the gut/oral microbiome, we can accelerate the growth toward a better global health based on precision medicine.
-
Ginsenoside Rg1 ameliorated experimental colitis by regulating the balance of M1/M2 macrophage polarization and the homeostasis of intestinal flora.
Aberrant M1/M2 macrophage polarization and dysbiosis are involved in the pathogenesis of ulcerative colitis (UC). Ginsenoside Rg1 exhibits optimal immunomodulatory and anti-inflammatory effects in treating UC of humans and animals, but the action mechanism through the regulation of M1/M2 macrophage polarization and intestinal flora composition remain unclear. Here, experimental colitis was induced in BALB/c mice using dextran sulfate sodium, and Rock1 inhibitor Y27632 was used to explore the action mechanism of ginsenoside Rg1. Following treatment with ginsenoside Rg1 (200 mg/kg/day) and Y27632 (10 mg/kg/day) for 14 consecutive days, the rate of change in mouse body weight, mouse final weight, colonic weight, colonic length, colonic weight index and pathological damage scores of colitis mice were effectively improved, accompanied by less ulcer formation and inflammatory cell infiltration, lower levels of interleukin (IL)-6, IL-33, chemokine (C-C motif) ligand 2 (CCL-2), tumor necrosis factor alpha (TNF-α), and higher IL-4 and IL-10. Importantly, ginsenoside Rg1 and Y27632 significantly down-regulated CD11b+F4/80+, CD11b+F4/80+Tim-1+ and CD11b+F4/80+TLR4+ macrophages, and CD11b+F4/80+iNOS+ M1 macrophages, and significantly up-regulated CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ M2 macrophages in colitis mice; concomitantly, ginsenoside Rg1 improved the diversity of colonic microbiota and regulated Lachnospiraceae, Staphylococcus, Bacteroide and Ruminococcaceae_UCG_014 at genus level in colitis mice, but the flora regulated by Y27632 was not identical to it. Moreover, ginsenoside Rg1 and Y27632 down-regulated the protein levels of Rock1, RhoA and Nogo-B in colitis mice. These results suggested that ginsenoside Rg1 and Y27632 ameliorated colitis by regulating M1/M2 macrophage polarization and microbiota composition, associated with inhibition of the Nogo-B/RhoA signaling pathway.
-
The Gut-Brain-Microbiome Connection: Can Probiotics Decrease Anxiety and Depression?
Anxiety and depression are highly prevalent mood disorders worldwide. Complete remission of symptoms is often difficult to achieve, despite following recommended treatment guidelines. Numerous antidepressants and anxiolytics exist, and new drugs are being developed constantly, yet the incidence of common mood disorders continues to rise. Despite the prevalence of these issues, mental health treatment has not evolved much in recent years. An exciting area of research uncovered in the past decade is the gut-brain-microbiome axis, a bi-directional communication pathway. Because the human microbiome is closely related to mood, research is being done to investigate whether probiotic supplementation could potentially affect symptoms of anxiety and depression.
-
A systematic review of the effects of probiotics on depression and anxiety: an alternative therapy?
This review aims to understand and analyse the effects of probiotics on depression, anxiety and psychological stress. These disorders are among the leading causes of disability worldwide. Conventional pharmacotherapies usually have a poor response or adverse side effects. In this context, recent studies have demonstrated a dense bi-directional communication named gut-brain axis. Evidences are demonstrating the relationship between disturbance in the enteric microbiome and psychiatric disorders, paving the way for the emergence of alternative therapies. A systematic search for randomized double/triple blind placebo-controlled clinical trials was performed in PubMed, Scopus and Lilacs. The studies selection followed the recommendations of the main items for report systematic reviews and meta-analyses (PRISMA). Nine articles met the criteria and were analysed for effects on depression, anxiety, psychological stress and biomarkers. Seven found positive results in at least one of the items. We concluded that the use of probiotics to alleviate depressive symptoms and anxiety is promising, mainly due to its potential anti-inflammatory effect, but additional and more rigorous double blind randomized clinical trials are necessary to endorse such conclusions.