Microbiome-targeted Therapies Research Articles

In situ targeted base editing of bacteria in the mouse gut.

Microbiome research is now demonstrating a growing number of bacterial strains and genes that affect our health1. Although CRISPR-derived tools have shown great success in editing disease-driving genes in human cells2, we currently lack the tools to achieve comparable success for bacterial targets in situ. Here we engineer a phage-derived particle to deliver a base editor and modify Escherichia coli colonizing the mouse gut. Editing of a β-lactamase gene in a model E. coli strain resulted in a median editing efficiency of 93% of the target bacterial population with a single dose. Edited bacteria were stably maintained in the mouse gut for at least 42 days following treatment. This was achieved using a non-replicative DNA vector, preventing maintenance and dissemination of the payload. We then leveraged this approach to edit several genes of therapeutic relevance in E. coli and Klebsiella pneumoniae strains in vitro and demonstrate in situ editing of a gene involved in the production of curli in a pathogenic E. coli strain. Our work demonstrates the feasibility of modifying bacteria directly in the gut, offering a new avenue to investigate the function of bacterial genes and opening the door to the design of new microbiome-targeted therapies.

Dynamic Human Gut Microbiome and Immune Shifts During an Immersive Psychosocial Therapeutic Program.

Depression is a leading cause of disability worldwide yet its underlying factors, particularly microbial associations, are poorly understood. We examined the longitudinal interplay between the microbiome and immune system in the context of depression during an immersive psychosocial intervention. 142 multi-omics samples were collected from 52 well-characterized participants before, during, and three months after a nine-day inquiry-based stress reduction program. We found that depression was associated with both an increased presence of putatively pathogenic bacteria and reduced microbial beta-diversity. Following the intervention, we observed reductions in neuroinflammatory cytokines and improvements in several mental health indicators. Interestingly, participants with a Prevotella-dominant microbiome showed milder symptoms when depressed, along with a more resilient microbiome and more favorable inflammatory cytokine profile, including reduced levels of CXCL-1. Our findings reveal a protective link between the Prevotella-dominant microbiome and depression, associated with a less inflammatory environment and moderated symptoms. These insights, coupled with observed improvements in neuroinflammatory markers and mental health from the intervention, highlight potential avenues for microbiome-targeted therapies in depression management.

Current landscape of fecal microbiota transplantation in treating depression.

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecal microbiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the long-term safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies.

Understanding Gut Health: Probiotics, Dysbiosis, and their Connection to Type 2 Diabetes - A Review

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by hyperglycaemia resulting from defects in insulin secretion, insulin action, or both. The pathophysiology of T2DM involves a multifaceted interplay of genetic, behavioural, and environmental factors. Beta cells play a central role in regulating blood glucose levels through intricate mechanisms involving insulin secretion triggered by elevated glucose concentrations and other factors. Dysfunction of beta cells in T2DM encompasses various molecular pathways influenced by factors such as hyperglycaemia, hyperlipidaemia, chronic inflammation, and genetic susceptibility, leading to impaired insulin secretion and insulin resistance. Recent research has highlighted the role of gut dysbiosis in the pathogenesis of T2DM, with alterations in gut microbiome composition impacting glucose metabolism. Dysbiosis-induced intestinal permeability can lead to systemic inflammation, contributing to insulin resistance and diabetes progression. Conversely, a diverse and rich gut microbiome has been associated with protection against obesity, diabetes, and metabolic syndrome. Probiotics, defined as live bacteria conferring health benefits when administered in adequate amounts, hold promise in mitigating T2DM-related metabolic derangements through various mechanisms, including modulation of gut microbiota, regulation of the gut-brain axis, and reduction of chronic low-grade inflammation. This provides a comprehensive overview of the mechanisms through which probiotics may positively impact glucose metabolism and discusses current evidence on the efficacy of probiotic supplementation in improving glycemic parameters and highlights the need for further research to elucidate strain-specific effects, optimal dosages, and long-term outcomes. Additionally, the translation of research findings into clinical practice and the potential of microbiome-targeted therapies for precision management of T2DM are explored, underscoring the importance of evidence-based guidelines for healthcare practitioners.

Modulation of Gut Microbial Biomarkers and Metabolites in Cancer Management by Tea Compounds.

Cancers are causing millions of deaths and leaving a huge clinical and economic burden. High costs of cancer drugs are limiting their access to the growing number of cancer cases. The development of more affordable alternative therapy could reach more patients. As gut microbiota plays a significant role in the development and treatment of cancer, microbiome-targeted therapy has gained more attention in recent years. Dietary and natural compounds can modulate gut microbiota composition while providing broader and more accessible access to medicine. Tea compounds have been shown to have anti-cancer properties as well as modulate the gut microbiota and their related metabolites. However, there is no comprehensive review that focuses on the gut modulatory effects of tea compounds and their impact on reshaping the metabolic profiles, particularly in cancer models. In this review, the effects of different tea compounds on gut microbiota in cancer settings are discussed. Furthermore, the relationship between these modulated bacteria and their related metabolites, along with the mechanisms of how these changes led to cancer intervention are summarized.

Probiotics, prebiotics, synbiotics and other microbiome-based innovative therapeutics to mitigate obesity and enhance longevity via the gut-brain axis

The global prevalence of obesity currently exceeds 1 billion people and is accompanied by an increase in the aging population. Obesity and aging share many hallmarks and are leading risk factors for cardiometabolic disease and premature death. Current anti-obesity and pro-longevity pharmacotherapies are limited by side effects, warranting the development of novel therapies. The gut microbiota plays a major role in human health and disease, with a dysbiotic composition evident in obese and aged individuals. The bidirectional communication system between the gut and the central nervous system, known as the gut-brain axis, may link obesity to unhealthy aging. Modulating the gut with microbiome-targeted therapies, such as biotics, is a novel strategy to treat and/or manage obesity and promote longevity. Biotics represent material derived from living or once-living organisms, many of which have therapeutic effects. Pre-, pro-, syn- and post-biotics may beneficially modulate gut microbial composition and function to improve obesity and the aging process. However, the investigation of biotics as next-generation therapeutics has only just begun. Further research is needed to identify therapeutic biotics and understand their mechanisms of action. Investigating the function of the gut-brain axis in obesity and aging may lead to novel therapeutic strategies for obese, aged and comorbid (e.g., sarcopenic obese) patient populations. This review discusses the interrelationship between obesity and aging, with a particular emphasis on the gut microbiome, and presents biotics as novel therapeutic agents for obesity, aging and related disease states.

The Potential Impact of the Gut Microbiota on Neonatal Brain Development and Adverse Health Outcomes.

Over the past decade, microbiome research has significantly expanded in both scope and volume, leading to the development of new models and treatments targeting the gut-brain axis to mitigate the effects of various disorders. Related research suggests that interventions during the critical period from birth to three years old may yield the greatest benefits. Investigating the substantial link between the gut and brain during this crucial developmental phase raises fundamental issues about the role of microorganisms in human health and brain development. This underscores the importance of focusing on the prevention rather than the treatment of neurodevelopmental and neuropsychiatric disorders. The present review examines the gut microbiota from birth to age 3, with a particular focus on its potential relationship with neurodevelopment. This review emphasizes the immunological mechanisms underlying this relationship. Additionally, the study investigates the impact of the microbiome on cognitive development and neurobehavioral issues such as anxiety and autism. Importantly, it highlights the need to integrate mechanistic studies of animal models with epidemiological research across diverse cultures to better understand the role of a healthy microbiome in early life and the implications of dysbiosis. Furthermore, this review summarizes factors contributing to the transmission of gut microbiome-targeted therapies and their effects on neurodevelopment. Recent studies on environmental toxins known to impact neurodevelopment are also reviewed, exploring whether the microbiota may mitigate or modulate these effects.

Roles of Traditional and Next-Generation Probiotics on Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH): A Systematic Review and Network Meta-Analysis.

Non-alcoholic fatty liver disease (NAFLD) and its progressive stage, non-alcoholic steatohepatitis (NASH), are becoming one of the most common chronic liver diseases globally. Lifestyle interventions such as weight reduction, increased physical activity, and maintaining healthy diets play a pivotal role in managing NAFLD/NASH. Recent studies suggest that the gut microbiome is associated with the pathogenesis of NAFLD/NASH, prompting microbiome-targeted therapy to emerge as a new therapeutic option for NAFLD/NASH. We conducted a systematic review based on the PRISMA statement and employed network meta-analysis to investigate the effects of traditional probiotics and next-generation probiotics (NGPs) on NAFLD/NASH. Comparative analysis reveals that traditional probiotics primarily reduce liver fat deposition and inflammation by improving gut microbiota composition, enhancing intestinal barrier function, and modulating immune responses. In contrast, NGPs demonstrate a more significant therapeutic potential, attributed to their direct effects on inhibiting oxidative stress and their ability to enhance the production of short-chain fatty acids (SCFAs), NGPs appear as a new potential strategy for the management of NAFLD/NASH through their dual action of directly inhibiting oxidative stress and enhancing SCFA production, highlighting the importance of understanding and utilizing the direct and indirect regulatory mechanisms of oxidative stress in the management of NAFLD/NASH.

Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.

The Value of Microbiome-targeted Therapy on Lipid Indices of Patients with Type 2 Diabetes Mellitus: An Umbrella Meta-analysis of Randomized Controlled Trials.

The current study aimed to investigate the impact of MTT on lipid indices of T2DM patients by performing an umbrella approach. Three international databases including PubMed, Scopus, and Web of Sciences were searched from inception up to April 2023 to find meta-analyses evaluating the impact of MTT (prebiotics, probiotics, and synbiotics) on the lipid profile of T2DM patients. Two independent researchers extracted data from the relevant meta-analyses. To find the source of heterogeneity various subgroup analyses were performed. Comprehensive Meta-Analyses (CMA) software version 3 was utilized for the final analysis. Based on the results of the current study MTT had a significant effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) (ES: - 0.092; 95%CI: -0.111, -0.074; P< 0.001, ES: -0.109; 95%CI: -0.137, -0.081; P< 0.001, ES: -0.036; 95%CI: -0.068, -0.005; P= 0.024, ES: 0.109; 95%CI: 0.056, 0.162; P<0.000, respectively). In subgroup analysis, probiotics showed the most substantial effect on all lipid biomarkers. This research has provided promising insights into the potential impact of MTT on lipid levels in patients diagnosed with T2DM. Notably, MTT had the greatest impact on HDL levels, followed by TG, TC, and LDL. As a result of our study, MTT is recommended as an adjunctive therapeutic option for T2DM treatment due to its capability to regulate lipid profiles.</p.

The Future of Atopic Dermatitis Treatment.

This chapter thoroughly examines recent breakthroughs in atopic dermatitis (AD) treatment, with a primary focus on the medications in the development pipeline. Biologics agents targeting new interleukin receptors like interleukin-31, interleukin-22, and interleukin-2 are discussed along with the novel pathway looking at the OX40-OX40L interaction. Oral agents and small molecule therapies like Janus kinase inhibitors, sphingosine-1-phosphate modulators, and Bruton's tyrosine kinase inhibitors are also discussed along with the various new topical medications. Newly approved topicals like phosphodiesterase-4 and JAK inhibitors are highlighted while also discussing the potential of tapinarof and emerging microbiome-targeted therapies. Beyond conventional approaches, the chapter touches upon unconventional therapies currently being studied. The goal of this chapter is to discuss new advances in AD treatment from medications in the initial stages of development to those nearing FDA approval.

Role of Microbiome in Personalized Medicine

The human microbiome, which consists of trillions of microorganisms residing in and on the human body, plays a significant role in personalized medicine. The microbiome has been recognized as a critical factor influencing various aspects of health and disease, and its consideration in personalized medicine is expanding. Factors such as genetics, diet, environment, and lifestyle contribute to the unique microbial profile of each person. Therefore, the microbiome varies between individuals in terms of its composition and diversity. The microbiome can influence drug metabolism and response. Some drugs undergo biotransformation by gut bacteria, affecting the pharmacokinetics and efficacy of the drugs. Understanding an individual's microbiome may help predict and optimize drug responses. The microbiome also plays a crucial role in shaping the immune system. Imbalances or dysbiosis in the microbiome have been linked to various immune-related disorders. Considering the microbiome in the development of immunotherapies and treatments for autoimmune diseases would help in developing personalized medicine. The bidirectional communication between the gut and the brain, known as the gut-brain axis, is influenced by the microbiome. The gut microbiome may impact neurological conditions, mental health, and even responses to certain medications. Personalized approaches may consider the gut-brain axis in neurological and psychiatric disorders. Similarly, alterations in the microbiome have been associated with various diseases, including inflammatory bowel disease, obesity, diabetes, and cancer. An individual's unique microbiome is crucial when designing personalized dietary recommendations. The microbiome influences metabolism, nutrient absorption, and overall health. Microbial biomarkers are being explored for disease diagnosis, prognosis, and treatment response. The identification of specific microbial signatures associated with certain conditions may aid in personalized diagnostics and treatment planning. Personalized medicine can help develop microbiome-targeted therapies, such as fecal microbiota transplantation or probiotics, to restore a healthy microbial balance in individuals with dysbiosis-related conditions. Computational models that integrate genetic, clinical, and microbiome data can be used to predict an individual's susceptibility to certain diseases or response to specific treatments. These models contribute to more precise and individualized medical care. The microbiome is an integral component of personalized medicine, influencing drug responses, immune function, and disease risk. Integrating microbiome data into personalized healthcare approaches has the potential to enhance diagnostic accuracy, treatment efficacy, and overall health outcomes for individuals. However, several challenges remain including the complexity of microbial interactions and the need for standardized methodologies. Ethical considerations, including privacy issues related to microbiome data, also need attention in the context of personalized medicine.

Fecal metabolite profiling identifies liver transplant recipients at risk for postoperative infection

Metabolites produced by the intestinal microbiome modulate mucosal immune defenses and optimize epithelial barrier function. Intestinal dysbiosis, including loss of intestinal microbiome diversity and expansion of antibiotic-resistant pathobionts, is accompanied by changes in fecal metabolite concentrations and increased incidence of systemic infection. Laboratory tests that quantify intestinal dysbiosis, however, have yet to be incorporated into clinical practice. We quantified fecal metabolites in 107 patients undergoing liver transplantation (LT) and correlated these with fecal microbiome compositions, pathobiont expansion, and postoperative infections. Consistent with experimental studies implicating microbiome-derived metabolites with host-mediated antimicrobial defenses, reduced fecal concentrations of short- and branched-chain fatty acids, secondary bile acids, and tryptophan metabolites correlate with compositional microbiome dysbiosis in LT patients and the relative risk of postoperative infection. Our findings demonstrate that fecal metabolite profiling can identify LT patients at increased risk of postoperative infection and may provide guideposts for microbiome-targeted therapies.

Microbiome-targeted interventions for the control of oral-gut dysbiosis and chronic systemic inflammation.

Recent research has confirmed the strong connection between imbalances in the oral and gut microbiome (oral-gut dysbiosis), periodontitis, and inflammatory conditions such as diabetes, Alzheimer's disease, and cardiovascular diseases. Microbiome modulation is crucial for preventing and treating several autoimmune and inflammatory diseases, including periodontitis. However, the causal relationships between the microbiome and its derived metabolites that mediate periodontitis and chronic inflammation constitute a notable knowledge gap. Here we review the mechanisms involved in the microbiome-host crosstalk, and describe novel precision medicine for the control of systemic inflammation. As microbiome-targeted therapies begin to enter clinical trials, the success of these approaches relies upon understanding these reciprocal microbiome-host interactions, and it may provide new therapeutic avenues to reduce the risk of periodontitis-associated diseases.

Advancements in Dermatological Therapies

Dermatology has witnessed remarkable advancements in therapeutic approaches, revolutionizing the field and transforming the landscape of skin health. From innovative treatment modalities to novel drug discoveries, the realm of dermatological therapies has expanded exponentially, offering new hope and improved outcomes for patients. These advancements have not only revolutionized the way we address various skin conditions but have also opened doors to personalized and targeted treatments. Exploring and embracing these advancements is crucial for dermatologists to provide the highest level of care and enhance the quality of life for their patients. The advent of biologics and targeted therapies has been a game-changer in dermatology. Conditions such as psoriasis, atopic dermatitis, and various autoimmune disorders now have targeted treatment options that specifically address the underlying mechanisms of the disease. Biologics, including monoclonal antibodies and immune modulators, have shown exceptional efficacy in managing these conditions, providing long-lasting relief and reducing disease burden for patients. Additionally, advancements in molecular research and genetic profiling have paved the way for personalized medicine in dermatology, allowing for tailored treatment plans based on an individual's unique genetic makeup and characteristics.&#x0D; Furthermore, technological innovations have brought forth significant advancements in dermatological therapies. Laser and light-based treatments have revolutionized the management of various skin conditions, including acne scars, vascular lesions, and unwanted pigmentation. These non-invasive procedures offer precise targeting and minimal downtime, delivering remarkable results with reduced risks. Moreover, the integration of artificial intelligence and digital health technologies has enhanced diagnostic accuracy and improved treatment outcomes. From teledermatology to image analysis algorithms, these technologies streamline patient care, facilitate remote consultations, and enable efficient data-driven decision-making.&#x0D; Collaborative efforts between dermatologists and pharmaceutical companies have also led to the development of novel therapeutic agents. New drug discoveries, formulations, and delivery systems have expanded treatment options for conditions such as skin cancer, fungal infections, and chronic inflammatory disorders. Researchers continue to explore innovative pathways, including immunotherapies and microbiome-targeted therapies, opening doors to further advancements in the field. Advancements in dermatological therapies have ushered in a new era of precision and effectiveness in the management of various skin conditions. From targeted biologics to technological innovations, these breakthroughs have transformed the way dermatologists approach patient care. Embracing these advancements and staying abreast of the latest developments is essential for dermatologists to provide the best possible care and improve patient outcomes. As the field continues to evolve, ongoing research, collaboration, and technological integration will shape the future of dermatological therapies, empowering both clinicians and patients in their pursuit of optimal skin health

Gut macrobiotic and its metabolic pathways modulate cardiovascular disease.

Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host's metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.

Do gut microbiome-targeted therapies improve liver function in cirrhotic patients? A systematic review and meta-analysis.

Microbiome-targeted therapies (MTTs) are considered as promising interventions for cirrhosis, but the impact of gut microbiome modulation on liver function and disease severity has not been fully assessed. We comprehensively evaluated the efficacy of MTTs in patients with liver cirrhosis. Data from randomized controlled trials were collected through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrial.gov from inception to February 20, 2023. Clinical outcomes were pooled and expressed in terms of risk ratios or mean differences (MD). Additional subgroup and sensitivity analyses were performed to validate the robustness of findings. A trial sequential analysis was applied to calculate the required information size and evaluate the credibility of the meta-analysis results. Twenty-one studies with a total of 1699 cirrhotic patients were included for meta-analysis. MTTs were associated with a significant reduction in aspartate aminotransferase (MD, -3.62; 95% CI, -6.59 to -0.65), the risk of hepatic encephalopathy (risk ratio=0.56, 95% CI: 0.46 to 0.68), model for end-stage liver disease score (MD, -0.90; 95% CI, -1.17 to -0.11), ammonia (MD, -11.86; 95% CI, -16.39 to -7.33), and endotoxin (MD, -0.14; 95% CI, -0.23 to -0.04). The trial sequential analysis yielded reliable results of these outcomes. No effects were observed on the changes of other hepatic function indicators. MTTs appeared to be associated with a slowed deterioration in liver cirrhosis, which could provide reference for clinicians in treatment of cirrhotic patients based on their conditions.

The impact of gut microbiome-targeted therapy on liver enzymes in patients with nonalcoholic fatty liver disease: an umbrella meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome-targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], -10.21; 95% confidence interval [CI], -13.29, -7.14; P < 0.001), aspartate aminotransferase (AST; ES, -8.86; 95%CI, -11.39, -6.32; P < 0.001), and γ-glutamyltransferase (ES, -5.56; 95%CI, -7.92, -3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, -8.69; 95%CI, -11.01, -6.37; P < 0.001) and ALT (ES, -9.82; 95%CI, -11.59, -8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, -11.40; 95%CI, -13.91, -8.88; P < 0.001) and ALT (ES, -11.87; 95%CI, -13.80, -9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, -2.96; 95%CI, -8.12, 2.18, P = 0.259; and ES, -4.69; 95%CI, -13.53, 4.15, P = 0.299, respectively). Gut microbiome-targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome-targeted therapies in the treatment of the NAFLD population. PROSPERO registration no. CRD42022346998.

Use of probiotics, prebiotics, and synbiotics in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Patients with non-alcoholic fatty liver disease (NAFLD) exhibit compositional changes in their gut microbiome, which represents a potential therapeutic target. Probiotics, prebiotics, and synbiotics are microbiome-targeted therapies that have been proposed as treatment for NAFLD. We aim to systematically review the effects of these therapies in liver-related outcomes of NAFLD patients. We conducted a systematic search in Embase (Ovid), Medline (Ovid), Scopus, Cochrane, and EBSCOhost from inception to August 19, 2022. We included randomized controlled trials (RCTs) that treated NAFLD patients with prebiotics and/or probiotics. We meta-analyzed the outcomes using standardized mean difference (SMD) and assessed study heterogeneity using Cochran's Q test and I2 statistics. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool. A total of 41 (18 probiotics, 17 synbiotics, and 6 prebiotics) RCTs were included. Pooled data demonstrated that the intervention had significantly improved liver steatosis (measured by ultrasound grading) (SMD: 4.87; 95% confidence interval [CI]: 3.27, 7.25), fibrosis (SMD: -0.61kPa; 95% CI: -1.12, -0.09kPa), and liver enzymes including alanine transaminase (SMD: -0.86U/L; 95% CI: -1.16, -0.56U/L), aspartate transaminase (SMD: -0.87U/L; 95% CI: -1.22, -0.52U/L), and gamma-glutamyl transferase (SMD: -0.77U/L; 95% CI: -1.26, -0.29U/L). Microbiome-targeted therapies were associated with significant improvements in liver-related outcomes in NAFLD patients. Nevertheless, limitations in existing literature like heterogeneity in probiotic strains, dosage, and formulation undermine our findings. This study was registered with PROSPERO (CRD42022354562) and supported by the Nanyang Technological University Start-up Grant and Wang Lee Wah Memorial Fund.

The Association between Gestational Diabetes and the Microbiome: A Systematic Review and Meta-Analysis.

Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and their offspring. The microbiota, the resident microbes within the body, have been linked to the development of several metabolic conditions. This systematic review with meta-analysis aims to summarize the evidence on the differences in microbiota composition in pregnant women with gestational diabetes and their offspring compared to healthy pregnancies. A thorough search was conducted in the PubMed, Scopus, and Web of Science databases, and data from 21 studies were analyzed utilizing 41 meta-analyses. In the gut microbiota, Bifidobacterium and Alistipes were found to be more abundant in healthy pregnancies, while Roseburia appears to be more abundant in gestational diabetes. The heterogeneity among study findings regarding the microbiota in the meconium is considerable. The placental microbiota exhibited almost no heterogeneity, with an increased abundance of Firmicutes in the gestational diabetes group and a higher abundance of Proteobacteria in the control. The role of the microbiota in gestational diabetes is reinforced by these findings, which additionally point to the potential of microbiome-targeted therapies. To completely comprehend the interactions between gestational diabetes and the microbiome, standardizing methodologies and further research is necessary.