Microbiota-targeted Interventions Research Articles

Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis

Background: The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome. Methods: This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits. Conclusions: In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.

The impact of a prebiotic-rich diet and/or probiotic supplements on human cognition: secondary outcomes from the ‘gut feelings’ randomised controlled trial

ABSTRACT Background Emerging evidence indicates that gut microbiota-targeted interventions may lead to improvements in cognition. We assessed whether a prebiotic-rich dietary intervention, probiotic supplement, or synbiotic combination of both would improve human cognition, as part of the ‘Gut Feelings’ trial. Methods An 8-week, 2 × 2 factorial randomised controlled trial was conducted on 118 adults with low mood and potential for dietary improvement. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). At baseline and 8-weeks, the Cogstate Brief Battery was administered, testing processing speed, attention, visual learning, and working memory. Data were analysed using Bayesian linear regression. Results We found weak evidence that the probiotic improved working memory (Cohen’s d = −0.32, 95% CI: –0.67, 0.03; posterior probability [post. prob] of benefit: 96%). For the other treatments, there was little or no evidence of cognitive improvement. We found weak evidence that the prebiotic diet impaired processing speed (d = 0.25, 95% CI: –0.02, 0.51; post. prob of harm: 97%). There was little indication of a synergistic interaction between the probiotic and prebiotic diet. Conclusion We found suggestive evidence of a probiotic-induced improvement in working memory, and prebiotic-induced impairment in processing speed. However, the evidence remains inconclusive regarding any cognitive benefit or harm induced by the probiotic, prebiotic diet, or synbiotic treatments. Larger intervention studies are recommended, with inclusion of neuroimaging or electrophysiology measures. Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN12617000795392; registered 31 May 2017).

Emerging Perspectives: The Interplay of Taste Perception and Oral Microbiota Composition in Dietary Preferences and Obesity.

Recent advancements in sensory research have brought to light the intricate relationship between taste perception and the oral microbiota, prompting investigations into their influence on human health, particularly in the context of dietary preferences and obesity. This review aims to update the current understanding of how oral microbiota influence taste perception and dietary choices, elucidating shared metabolic pathways between food processing and oral bacteria. Further, this review outlines the mechanisms underlying taste perception, emphasizing the role of taste receptors and taste buds in shaping sensory experiences influenced by genetic and environmental factors. Notably, we explore the bidirectional relationship between oral microbiota and taste sensitivity, highlighting the potential impact of microbial composition on taste perception thresholds and implications for dietary habits and health outcomes, such as obesity and dental caries. However, significant research gaps remain, particularly in the understanding of the molecular mechanisms linking oral microbiota with taste sensitivity, as well as the long-term effects of microbiota-targeted interventions. Future research should focus on longitudinal studies and experimental interventions to explore these connections more deeply, offering insights into potential strategies for promoting healthier dietary behaviors and managing diet-related non-communicable diseases.

The Microbiota and Microbiome in COVID-19 in Adults and Children and Potential Therapeutic Interventions: A Review

The work presented is a comprehensive review of the role of the human microbiota in the context of the COVID-19 pandemic. A diverse microbial community heavily colonizes the human body called the microbiota, with the gut microbiota being the most diverse. The composition of the microbiota varies in different parts of the body and changes with age, diet, and other environmental factors. Emerging evidence suggests that the gut microbiota plays a critical role in modulating the host immune response and may influence the severity of COVID-19. Patients with COVID-19 have significant alterations in their gut and respiratory microbiota, characterized by a depletion of beneficial commensal bacteria and an enrichment of opportunistic pathogens. These changes in microbiota composition are associated with elevated inflammatory markers, a dysregulated immune response, and more severe disease outcomes. In addition, changes in the gut microbiota can affect lung and brain function, influencing the severity of COVID-19 cases and neurological symptoms, as well as long-term neurological complications associated with the disease. Due to the importance of the microbiota in COVID-19, several therapeutic approaches targeting the microbiota have been proposed to improve outcomes in this disease, including fecal microbiota transplantation, probiotic and prebiotic supplementation, postbiotic or microbiota-derived metabolite supplementation, dietary interventions, and lifestyle strategies. Overall, the review highlights the critical role of the human microbiota in the pathogenesis and progression of COVID-19 and the potential of microbiota-targeted interventions to improve patient outcomes. HIGHLIGHTS COVID-19 causes gut microbiota dysbiosis, associated with elevated inflammatory markers, a dysregulated immune response, and more severe disease outcomes. Gut microbiota dysbiosis due to COVID-19 affects lung and brain function, which is associated with the severity of COVID-19 cases. Gut microbiota is crucial in COVID-19, so several strategies have been developed to regulate it in COVID-19 cases, such as fecal microbiota transplantation, probiotics, and prebiotics, among others. GRAPHICAL ABSTRACT

Microbiota-targeted interventions and clinical implications for maternal-offspring health: An umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Microbes in the human body are the determinants of life-long health and disease. Microbiome acquisition starts in utero and matures during early childhood through breastfeeding. However, maternal gut dysbiosis affects the maternal-offspring microbiome interplay. Lines of evidence on dysbiosis-targeted interventions and their effect on maternal-offspring health and gut microbiome are inconsistent and inconclusive. Therefore, this study summarised studies to identify the most common microbiota-targeted intervention during pregnancy and lactation and to comprehensively evaluate its effects on maternal and offspring health. This umbrella review was conducted by systematically searching databases such as PubMed and the Web of Science from inception to 2 September 2023. The quality was assessed using the Assessment of Multiple Systematic Reviews-2 checklist. The Grading of Recommendations Assessment, Development, and Evaluation was used for grading the strength and certainty of the studies. The overlap of primary studies was quantified by the corrected covered area score. A total of 17 systematic reviews and meta-analyses with 219 randomised controlled trials, 39 113 mothers, and 20 915 infants were included in this study. About 88% of studies had moderate and above certainty of evidence. Probiotics were the most common and effective interventions at reducing gestational diabetes risk (fasting blood glucose with the mean difference (MD) = -2.92, -0.05; I2 = 45, 98.97), fasting serum insulin (MD = -2.3, -2.06; I2 = 45, 77), glycated haemoglobin (Hb A1c) = -0.16; I2 = 0.00)), Homeostatic Model Assessment of insulin resistance (HOMA-IR) (MD = -20.55, -0.16; I2 = 0.00, 72.00), and lipid metabolism (MD = -5.47, 0.98; I2 = 0.00, 90.65). It was also effective in preventing and treating mastitis (risk ratio (RR) = 0.49; I2 = 2.00), relieving anxiety symptoms (MD = -0.99, 0.01; I2 = 0.00, 70.00), depression in lactation (MD = -0.46, -0.22; I2 = 0.00, 74.00) and reducing recto-vaginal bacterial colonisation (odds ratio (OR) = 0.62; I2 = 4.80), and with no adverse events. It also effectively remodelled the infant gut microbiome (MD = 0.89; I2 = 95.01) and prevented infant allergies. However, studies on pregnancy outcomes and preeclampsia incidences are limited. Our findings from high-quality studies identify that probiotics are the most common microbiome interventions during pregnancy and lactation. Probiotics have a strong impact on maternal and offspring health through maintaining gut microbiome homeostasis. However, further studies are needed on the effect of microbiota-targeted interventions on maternal cardiometabolic health, pregnancy, and neonatal outcomes. This umbrella review was registered with PROSPERO, CRD42023437098.

The Impact of the Middle Ear Microbiota on Otitis Media Outcomes: A Meta-Analysis of Longitudinal Studies

Introduction: Otitis media (OM), a prevalent middle ear inflammation, often involves microbial colonization. The composition of the middle ear microbiota may influence OM outcomes, including recurrence, persistence, and treatment response. This meta-analysis investigated the relationship between the middle ear microbiota and OM outcomes. Methods: Longitudinal studies published from 2018 to 2024 that explored the middle ear microbiota and OM outcomes were systematically searched in PubMed, Embase, and Web of Science. Data on study design, participant characteristics, microbiota analysis, and OM outcomes were extracted. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used to pool effect estimates. Results: A total of 15 studies (n = 2,540 participants) met the inclusion criteria. The middle ear microbiota diversity was significantly lower in children with recurrent OM compared to those without (standardized mean difference [SMD] = -0.45, 95% confidence interval [CI] -0.62 to -0.28, p < 0.001). The presence of specific pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, was associated with an increased risk of OM recurrence (odds ratio [OR] 1.75, 95% CI 1.32 to 2.31, p < 0.001). Additionally, microbial dysbiosis was associated with delayed resolution of OM and increased antibiotic treatment failure. Conclusion: The middle ear microbiota composition significantly impacts OM outcomes. Reduced diversity and specific pathogens are associated with increased OM recurrence. These findings highlight the potential for microbiota-targeted interventions in OM management.

Behavioral dysregulation in Nile tilapia (Oreochromis niloticus, GIFT) post-Streptococcus agalactia infection: Role of the microbiota-gut-brain axis

In the aquatic farming industry, understanding the factors affecting fish behavior is crucial, particularly in response to infections that compromise welfare and productivity. Swimming performance is a key life history trait critical to their ecology. This study explores the swimming behavior imbalance in Nile tilapia (Oreochromis niloticus, GIFT) post-infection with Streptococcus agalactiae (GBS), a common pathogen responsible for significant losses in aquaculture. We focused on how the microbiota-gut-brain axis influences the behavioral response of tilapia to GBS infection. Behavioral changes were quantified by measuring collision times and swimming speeds, which decreased significantly following infection. This behavioral downturn is mediated by alterations in the microbiota-gut-brain axis, evidenced by increased levels of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the brain and intestinal tissues. The study utilized pharmacological agents, the 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635), to investigate their efficacy in mitigating these behavioral and biochemical changes. Both agents partially restored normal behavior by adjusting neurotransmitter concentrations disrupted by GBS infection. Additionally, a notable increase in the relative abundance of Streptococcus within the gut microbiota of infected fish highlights the potential role of specific bacterial populations in influencing host behavior. This research provides novel insights into the complex interactions between pathogen-induced gut microbiota changes and Nile tilapia's behavioral outcomes, highlighting potential avenues for improving fish health management through microbiota-targeted interventions.

The metabolic and endocrine impact of diet-derived gut microbiota metabolites on ageing and longevity

Gut dysbiosis has been recently recognized as a hallmark of ageing. At this stage of life, gut microbiota becomes depleted from bacteria involved in the production of short-chain fatty acids (SCFA), indole and its derivative indole-3-propionic acid (IPA), metabolites shown to improve host glycemic control as well as insulin sensitivity and secretion. Moreover, gut microbiota becomes enriched in pathobiont bacteria involved in the production of imidazole propionate, phenols and trimethylamine, metabolites that promote host insulin resistance and atherosclerosis. The magnitude of these changes is much more pronounced in unhealthy than in healthy ageing. On the other hand, a distinct gut microbiota signature is displayed during longevity, the most prominent being an enrichment in both SCFA and IPA bacterial producers. This short Review discusses, in an innovative and integrative way, cutting-edge research on the composition of gut microorganisms and profile of metabolites secreted by them, that are associated with a healthy and unhealthy ageing pattern and with longevity. A detailed description of the positive or detrimental metabolic effects, in the ageing host, of diet-derived gut microbial metabolites is provided. Finally, microbiota-targeted interventions that counteract gut dysbiosis associated with ageing, are briefly outlined.

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice

BackgroundRecent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. ObjectiveThis study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. MethodsGerm-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. ResultsMaternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. ConclusionsThe presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.

Is There an Interplay between Environmental Factors, Microbiota Imbalance, and Cancer Chemotherapy-Associated Intestinal Mucositis?

Interindividual variation in drug efficacy and toxicity is a significant problem, potentially leading to adverse clinical and economic public health outcomes. While pharmacogenetics and pharmacogenomics have long been considered the primary causes of such heterogeneous responses, pharmacomicrobiomics has recently gained attention. The microbiome, a community of microorganisms living in or on the human body, is a critical determinant of drug response and toxicity. Factors such as diet, lifestyle, exposure to xenobiotics, antibiotics use, illness, and genetics can influence the composition of the microbiota. Changes in the intestinal microbiota are particularly influential in drug responsiveness, especially in cancer chemotherapy. The microbiota can modulate an individual's response to a drug, affecting its bioavailability, clinical effect, and toxicity, affecting treatment outcomes and patient quality of life. For instance, the microbiota can convert drugs into active or toxic metabolites, influencing their efficacy and side effects. Alternatively, chemotherapy can also alter the microbiota, creating a bidirectional interplay. Probiotics have shown promise in modulating the microbiome and ameliorating chemotherapy side effects, highlighting the potential for microbiota-targeted interventions in improving cancer treatment outcomes. This opinion paper addresses how environmental factors and chemotherapy-induced dysbiosis impact cancer chemotherapy gastrointestinal toxicity.

Comment on, “Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes”

The article “Characterization of oral microbiota in HPV and non-HPV head and neck squamous cell carcinoma and its association with patient outcomes” by Chan et al. investigates the relationship between oral microbiota, HPV infection, and patient outcomes in head and neck squamous cell carcinoma (HNSCC). This comprehensive study, involving 166 Chinese adults, utilized advanced sequencing techniques to profile bacterial and HPV regions in paired tumor and control tissues. The findings highlight the complex interplay between microbiota dysbiosis, HPV infection, and HNSCC progression. Despite the robustness of the study, limitations include potential biases in DNA extraction and PCR amplification, and unaccounted environmental factors. Recommendations for future research include increasing sequencing depth, comparing DNA extraction methods, using multiple bioinformatics pipelines, and controlling for environmental variables. Longitudinal studies and microbiota-targeted interventions are suggested to further elucidate the role of oral microbiota in HNSCC and improve patient outcomes.

Investigating the bacterial profiles of Lactobacillus, Bifidobacterium, Actinobacteria, Fusobacterium, Firmicutes, and Bacteroides in stool samples from patients with severe depression and healthy individuals

Depression is a multifaceted mental health disorder with complex etiology and significant global burden. Recent research indicates that the gut microbiota plays a role in the pathophysiology of depression, highlighting the potential role of specific bacterial species in influencing mood and cognitive function. In this study, we aimed to investigate the presence, copy numbers, and Ct values of selected bacterial species in stool samples from depressed patients (n=50) compared to control subjects (n=50). Our findings revealed significant differences in the abundance of Fusobacterium spp., Bifidobacterium spp., Lactobacillus spp., Bacteroidetes phylum, Firmicutes phylum, and Actinobacteria spp. between the two groups. Dysregulation of the gut microbiota, characterized by decreased presence of beneficial bacteria (e.g., Bifidobacterium spp., Lactobacillus spp.) and altered abundance of potentially pathogenic bacteria (e.g., Fusobacterium spp.), may contribute to the development or exacerbation of depression. These findings support the emerging concept of the gut-brain axis and its role in mental health. However, further research is needed to better understand the underlying mechanisms and explore the therapeutic potential of microbiota-targeted interventions for depression. Understanding the intricate interplay between the gut microbiota and depression could pave the way for novel treatment strategies and personalized approaches in mental health care.

Gut-Brain Axis: Investigating the Effects of Gut Health on Cognitive Functioning in Adults.

The gut-brain axis is a bidirectional communication network linking the gastrointestinal tract and the central nervous system via neuronal, hormonal, and antibody signaling pathways. Central to this connection is gut health, encompassing the balance and functionality of gut microbiota, which significantly impacts on mental and cognitive health. This study investigates the association between gut health and cognitive functioning in adults, highlighting the mechanisms by which gut microbiota influence brain health. To examine the effects of gut health on adult cognitive performance, with a focus on the processes by which gut microbiota impacts brain health. A quantitative cross-sectional study was conducted in Islamabad from January 2024 to April 2024, involving 140 adult participants. Data were collected using a comprehensive 16-item gut health questionnaire and the cognition self-assessment rating scale (C-SARS). The psychometric properties of these scales were assessed, and the data were analyzed using Statistical Product and Service Solutions (SPSS, v26; IBM SPSS Statistics for Windows, Armonk, NY). Analytical and descriptive statistics, including regression, chi-square, independent sample t-tests, and mean and standard deviation, were applied. The study found moderate associations between gut health and cognitive performance, particularly in memory and processing speed (R² = 0.17, β = -1.9, p = 0.12 for general cognition; R² = 0.01, β = -0.98, p = 0.02 for memory; R² = 0.03, β = -0.18, p = 0.03 for processing speed). Gender and marital status differences were significant, with males exhibiting better gut health scores than females (M = 34.1, SD = 3.2 vs. M = 31.2, SD = 3.2, p = 0.00), and singles showing better cognitive performance compared to married individuals (M = 9.4, SD = 5.4 vs. M = 6.5, SD = 3.7, p = 0.03). The study highlights significant associations between gut health and cognitive functions, suggesting that gut microbiota composition can influence cognitive performance. Gender and marital status differences underscore the need to consider individual differences in gut-brain axis research. Future studies should replicate these findings in larger samples and explore gut microbiota-targeted interventions for cognitive health enhancement.

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.

Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.

Deciphering the gut microbiota's (Coprococcus and Subdoligranulum) impact on depression: Network pharmacology and molecular dynamics simulation

Depression, a prevalent mental health condition, significantly impacts global mental impairment rates. While antidepressants are commonly used, treatment-resistant depression (TRD) poses a challenge. Emerging research highlights the role of the gut microbiota in depression through the gut-brain axis. This study identifies key genes associated with depression influenced by specific gut microbiota, Coprococcus and Subdoligranulum. Using bioinformatics tools, potential targets were elucidated, and molecular docking studies were performed. Furthermore, gene expression analysis identified hub-genes related to depression, intersecting with metabolite targets. Protein-protein interaction analysis revealed pivotal targets such as PTGS2 and MMP9. Molecular docking demonstrated 3-Indolepropionic acid's superior affinity over (R)-3-(4-Hydroxyphenyl)lactate. Physicochemical properties and toxicity profiles were compared, suggesting favorable attributes for 3-Indolepropionic acid. Molecular dynamics simulations confirmed stability and interactions of compounds with target proteins. This comprehensive approach sheds light on the complex interplay between gut microbiota, genes, and depression, emphasizing the potential for microbiota-targeted interventions in mental health management.

Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.

This mini-review explores the role of short-chain fatty acids (SCFAs) in posttraumatic stress disorder (PTSD). Highlighting the microbiota-gut-brain axis, this study investigated the bidirectional communication between the gut microbiome and mental health. SCFAs, byproducts of gut microbial fermentation, have been examined for their potential impact on PTSD, with a focus on molecular mechanisms and therapeutic interventions. This review discusses changes in SCFA levels and bacterial profiles in individuals with PTSD, emphasizing the need for further research. Promising outcomes from clinical trials using probiotics and fermented formulations suggest potential avenues for PTSD management. Future directions involve establishing comprehensive human cohorts, integrating multiomics data, and employing advanced computational methods, with the goal of deepening our understanding of the role of SCFAs in PTSD and exploring microbiota-targeted interventions.

The Effect of Gut Microbiota-Targeted Interventions on Neuroinflammation and Motor Function in Parkinson's Disease Animal Models-A Systematic Review.

Gut microbiome-targeted interventions such as fecal transplant, prebiotics, probiotics, synbiotics, and antibiotic gut depletion are speculated to be of potential use in delaying the onset and progression of Parkinson's disease by rebalancing the gut microbiome in the context of the gut-brain axis. Our study aims to organize recent findings regarding these interventions in Parkinson's disease animal models to identify how they affect neuroinflammation and motor outcomes. A systematic literature search was applied in PubMed, Web of Science, Embase, and SCOPUS for gut microbiome-targeted non-dietary interventions. Studies that investigated gut-targeted interventions by using in vivo murine PD models to follow dopaminergic cell loss, motor tests, and neuroinflammatory markers as outcomes were considered to be eligible. A total of 1335 studies were identified in the databases, out of which 29 were found to be eligible. A narrative systematization of the resulting data was performed, and the effect direction for the outcomes was represented. Quality assessment using the SYRCLE risk of bias tool was also performed. Out of the 29 eligible studies, we found that a significant majority report that the intervention reduced the dopaminergic cell loss (82.76%, 95% CI [64.23%, 94.15%]) produced by the induction of the disease model. Also, most studies reported a reduction in microglial (87.5%, 95% CI [61.65%, 98.45%]) and astrocytic activation (84,62%, 95% CI [54.55%, 98.08%]) caused by the induction of the disease model. These results were also mirrored in the majority (96.4% 95% CI [81.65%, 99.91%]) of the studies reporting an increase in performance in behavioral motor tests. A significant limitation of the study was that insufficient information was found in the studies to assess specific causes of the risk of bias. These results show that non-dietary gut microbiome-targeted interventions can improve neuroinflammatory and motor outcomes in acute Parkinson's disease animal models. Further studies are needed to clarify if these benefits transfer to the long-term pathogenesis of the disease, which is not yet fully understood. The study had no funding source, and the protocol was registered in the PROSPERO database with the ID number CRD42023461495.

Diet, Gut Physiology, and the Microbiota-Gut-Brain Axis

Diet is a large influencer of the gut microbiota composition and function across the lifespan. However, information on whether and how diet can affect the brain via bidirectional communication between the gut and the central nervous system (the microbiota-gut-brain axis) is emerging. Immune, endocrine, humoral, and neural connections between the gastrointestinal tract and the central nervous system are important to this axis. The gut microbiota can produce cytokines, neurotransmitters, neuropeptides, chemokines, endocrine messengers, and microbial metabolites (e.g., short-chain fatty acids, branched chain amino acids, and peptidoglycans), some of which can enter the brain, influencing the function of brain cells. Animal studies investigating the potential of nutritional interventions on this axis have advanced our understanding of the role of diet in this bidirectional communication. This includes insights into microbial metabolites, immune, neuronal, and metabolic pathways amendable to dietary modulation. However, several aspects of the gastrointestinal tract and brain of animal models differ to humans, and it is important to consider these differences and similarities when evaluating the transability of the findings to the human context. Randomised clinical trials using dietary interventions in humans in this field are limited but have high potential application for clinical nutrition. In particular, several microbiota-targeted interventions have been explored as potential approaches for mental health. These approaches include probiotics, prebiotics, etc. as well as dietary approaches(1,2,3). However, there are limited clinical interventions with whole-dietary approaches. Most human studies used faecal samples to infer changes in microbiota parameters occurring in the gastrointestinal tract and do not consider the physiological changes in gastrointestinal physiology (e.g., transit time) that can directly or indirectly affect the diversity and composition of the gut microbiome. Future research considerations should include better characterisation of the participants at baseline (dietary patterns, gastrointestinal phenotype, and gut microbiota composition) to identify potential responders to dietary interventions. In addition to gut microbiota assessment, evaluations of physiological parameters, brain function and behavioural measurements should be considered as part of the study protocol. In this presentation, the current state of the literature triangulating the diet, the gut microbiota, and host behaviour/brain processes will be addressed. Future research considerations will also be discussed.

Gut Microbiota and Its Implications for Cardiovascular Diseases – a Review

Background: The symbiotic relationship between the gut microbiota and cardiovascular health has become a main point in contemporary research, offering valuable insights into the pathogenesis of cardiovascular diseases (CVDs). This review aims to comprehensively examine the bidirectional communication between gut microbial communities and the cardiovascular system, explaining the intricate mechanisms that connect gut dysbiosis to the initiation and progression of CVDs.&#x0D; Material and Methods: A systematic literature review was conducted to compile and analyze relevant studies investigating the impact of the gut microbiota on cardiovascular health. Emphasis was placed on explaining the molecular and physiological mechanisms underlying the interaction between gut microbes and cardiovascular function.&#x0D; Results: Our review confirmed evidence linking gut microbiota-derived metabolites, such as short-chain fatty acids, trimethylamine N-oxide and lipopolysaccharides to vascular function and inflammation. Additionally, we explored the modulation of host metabolism and immune responses by gut microbes, providing insights into their roles in atherosclerosis and hypertension. The review highlight the influence of diet and lifestyle on shaping the gut microbiome and, consequently, cardiovascular outcomes.&#x0D; Conclusions: Gut microbiota plays a crucial role in cardiovascular health and is involved in the start and development of various heart diseases. The identified molecular and physiological mechanisms highlight the need for complete understanding of the gut-cardiovascular axis. Moreover, the review emphasizes the potential of microbiota-targeted interventions, including probiotics and fecal microbiota transplantation, as innovative strategies for preventing and managing CVDs.

Probiotics for adults with major depressive disorder compared with antidepressants: a systematic review and network meta-analysis.

Despite recent advances in antidepressants in treating major depression (MDD), their usage is marred by adverse effects and social stigmas. Probiotics may be an efficacious adjunct or standalone treatment, potentially circumventing the aforementioned issues with antidepressants. However, there is a lack of head-to-head clinical trials between these 2 interventions. A systematic review and network meta-analysis was conducted to compare the efficacy and acceptability of these 2 interventions in treating MDD. Six databases and registry platforms for the clinical trial were systematically searched to identify the eligible double-blinded, randomized controlled trials published between 2015 and 2022. Two authors selected independently the placebo-controlled trials of antidepressants and microbiota-targeted interventions (prebiotics, probiotics, and synbiotics) used for the treatment of MDD in adults (≥18 years old). Standardized mean differences (SMDs) of depressive symptom scores from individual trials were pooled for network meta-analysis (PROSPERO no. CRD42020222305). Forty-two eligible trials covering 22 interventions were identified, of which 16 were found to be effective in MDD treatment and the certainty of evidence was moderate to very low. When all trials were considered, compared with placebo, SMDs of interventions ranged from -0.16 (95% credible interval: -0.30, -0.04) for venlafaxine to -0.81 (-1.06, -0.52) for escitalopram. Probiotics were superior to brexpiprazole (SMD [95% credible interval]: -0.42 [-0.68, -0.17]), cariprazine (-0.44 [-0.69, -0.24]), citalopram (-0.37 [-0.66, -0.07]), duloxetine (-0.26, [-0.51, -0.04]), desvenlafaxine (-0.38 [-0.63, -0.14]), ketamine (-0.32 [-0.66, -0.01]), venlafaxine (-0.47 [-0.73, -0.23]), vilazodone (-0.37 [-0.61, -0.12]), vortioxetine (-0.39 [-0.63, -0.15]), and placebo (-0.62 [-0.86, -0.42]), and were noninferior to other antidepressants. In addition, probiotics ranked the second highest in the treatment hierarchy after escitalopram. Long-term treatment (≥8 weeks) using probiotics showed the same tolerability as antidepressants. Probiotics, compared with antidepressants and placebo, may be efficacious as an adjunct or standalone therapy for treating MDD. PROSPERO registration no. CRD42020222305.