Influence of Maqian essential oil on gut microbiota and immunoresponses in type 1 diabetes: In silico study.

Diversity and homeostasis of gut bacterial composition is highly associated with the pathogenesis of insulin dysfunction and type 1 diabetes melittus (T1D), hence emerged in parallel with the activation of autoimmunity. We aimed to study the bioactive potential of essential oil from Zanthoxylum myriacanthum var. pubescens Huang (Maqian) through computational approaches. Twelve chemical constituents derived from Maqian essential oil were docked with selected proteins (i.e., 3pig, 1kho, 7dmq, 4m4d, 2z65, 4glp, and 3fxi) in which are involved in gut microbiota modulation in T1D. Subsequently, the prediction of bioavailability properties of the small molecules were evaluated. Among all chemical constituents, the post-docking interaction analysis demonstrated that α-phellandrene exhibits the strongest binding affinity and induces gut microbiota modulation with ß-fructofuranosidase from Bifidobacterium longum. The current result revealed the potential of 3-Carene and α-Pinene in inducing specific changes in gut microbiota downregulating Clostridium perfringens and quenching Leptotrichia shahii respectively. ß-Pinene possess exceptionally strong binding affinity that effectively disrupt the interaction between lipopolysaccharide and its cognate receptors, while α-Phellandrene was exhibited the uppermost binding affinity with TLR4/MD2 and could likely target TLR4 stimulating lipopolysaccharide. Our results are the first to report on the gut microbiota modulation effects of α-Phellandrene and ß-Phellandrene via actions on LPS binding to CD14 and the TLR4 co-receptor signaling. In conclusion, our findings based on computational approaches, small molecules from Maqian present as promising agents which could regulate inflammatory response and modulate gut microbiota in type 1 diabetes mellitus.

Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management.

Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.

The anti-melanogenic properties of Swietenia macrophylla king.

Fair flawless skin is the goal for some cultures and the development of irregular skin pigmentation is considered an indication of premature skin aging. Hence, there is a rising demand for skin whitening cosmetics. Thus, this research will be focusing on discovering the anti-pigmentation properties of Swietenia macrophylla seeds. Firstly, the seeds were extracted with ethanol and further fractionate based on their polarity before testing them on zebrafish embryos. The ethanolic extract of the seed demonstrated significant inhibition of both tyrosinase activity and melanin production in the embryos. However, after fractionation, the anti-melanogenic ability was observed to have decreased, signifying that the phytocompounds may be synergistic in nature. Still in the proteomic studies the ethanolic extract and its hexane fraction both induced the downregulation of cathepsin LB and cytoskeletal proteins that have connections to the melanogenic pathway, confirming that S. macrophylla seeds do indeed have anti-pigmentation properties that can be exploited for cosmetic use. Next, limonoids (tetranortriterpenoids found in the seed) were tested for their inhibitory effect against human tyrosinase related protein 1 (TYRP-1) via molecular docking. It was found that limonoids have a stronger binding affinity to TYRP-1 than kojic acid, suggesting that these phytocompounds may have the potential in inhibiting pigmentation. However, this still needs further confirmation before these phytocompounds can be developed into a skin whitening agent. Other assays like ex-vivo or 3D human skin culture can also be used to better study the seeds anti-pigmentation effect on humans.

The Emerging Role of MMP12 in the Oral Environment.

Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.

Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review.

Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.

On an Affordable Approach towards the Diagnosis and Care for Prostate Cancer Patients Using Urine, FTIR and Prediction Machines.

Prostate cancer is a widespread form of cancer that affects patients globally and is challenging to diagnose, especially in its early stages. The common means of diagnosing cancer involve mostly invasive methods, such as the use of patient's blood as well as digital biopsies, which are relatively expensive and require a considerable amount of expertise. Studies have shown that various cancer biomarkers can be present in urine samples from patients who have prostate cancers; this paper aimed to leverage this information and investigate this further by using urine samples from a group of patients alongside FTIR analysis for the prediction of prostate cancer. This investigation was carried out using three sets of data where all spectra were preprocessed with the linear series decomposition learner (LSDL) and post-processed using signal processing methods alongside a contrast across nine machine-learning models, the results of which showcased that the proposed modeling approach carries potential to be used for clinical prediction of prostate cancer. This would allow for a much more affordable and high-throughput means for active prediction and associated care for patients with prostate cancer. Further investigations on the prediction of cancer stage (i.e., early or late stage) were carried out, where high prediction accuracy was obtained across the various metrics that were investigated, further showing the promise and capability of urine sample analysis alongside the proposed and presented modeling approaches.

Salt-Sensitive Ileal Microbiota Plays a Role in Atrial Natriuretic Peptide Deficiency-Induced Cardiac Injury.

Atrial natriuretic peptide (ANP) activity deficiency contributes to salt-sensitive hypertension in humans and mice. However, the role of ileal microbiota in salt sensitivity in ANP deficiency-related cardiac injury has not been investigated yet. This study used ANP-/- mice to analyze the role of the salt-sensitive ileal microbiome on cardiac injury. ANP-/- mice showed an increase in blood pressure (BP), the heart weight/body weight (HW/BW) ratio, and cardiac hypertrophy compared with wild-type (WT) mice. ANP deficiency did not impact the histological structure but reduced occludin expression in the ileum. Antibiotics significantly relieved BP and cardiac hypertrophy in ANP-/- mice. A high-salt diet (HSD) increased BP, the HW/BW ratio, and cardiac hypertrophy/fibrosis in WT and ANP-/- mice, and an HSD treatment in ANP-/- mice exacerbated these cardiac parameters. The HSD markedly decreased muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of WT and ANP-/- mice. Furthermore, the HSD increased the level of TLR4 and IL-1ß in ANP-/- mice ileum compared with WT mice. Antibiotics reduced the HW/BW ratio, cardiac hypertrophy/fibrosis, and the level of TLR4 and IL-1ß in the ileum, and rescued the muscularis layer thickening, villus length, and numbers of Paneth and goblet cells in the ileum of HSD-ANP-/- mice. Importantly, ANP deficiency induced the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum on the NSD diet, which was only observed in HSD-induced WT mice but not in WT mice on the NSD. Besides, the HSD significantly enhanced the sum of the percentage of the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum of ANP-/- mice. Ileal microbiota transfer (IMT) from ANP-/- mice to healthy C57BL/6J mice drove Lactobacillus johnsonii and Lactobacillus reuteri colonization in the ileum, which manifested an increase in BP, the HW/BW ratio, cardiac hypertrophy, and ileal pathology compared with IMT from WT mice. The HSD in C57BL/6J mice with IMT from ANP-/- mice drove the colonization of Burkholderiales bacterium YL45, Lactobacillus johnsonii, and Lactobacillus reuteri in the ileum and further exacerbated the cardiac and ileal pathology. Our results suggest that salt-sensitive ileal microbiota is probably related to ANP deficiency-induced cardiac injury.

The Prospects of Swietenia macrophylla King in Skin Care.

The importance of cosmetics in our lives is immeasurable. Covering items from daily personal hygienic products to skincare, it has become essential to consumers that the items that they use are safe and effective. Since natural products are from natural sources, and therefore considered "natural" and "green" in the public's eyes, the rise in demand for such products is not surprising. Even so, factoring in the need to remain on trend and innovative, cosmetic companies are on a constant search for new ingredients and inventive new formulations. Based on numerous literature, the seed of Swietenia macrophylla has been shown to possess several potential "cosmetic-worthy" bioproperties, such as skin whitening, photoprotective, antioxidant, antimicrobial, etc. These properties are vital in the cosmetic business, as they ultimately contribute to the "ageless" beauty that many consumers yearn for. Therefore, with further refinement and research, these active phytocompounds may be a great contribution to the cosmetic field in the near future.

Design and synthesis of quinolinium-based derivatives targeting FtsZ for antibacterial evaluation and mechanistic study.

The discovery of small molecular inhibitors targeting essential and conserved bacterial drug targets such as FtsZ protein is a promising approach to fight against multi-drug resistant bacteria. In the present study, two new series of FtsZ inhibitors based on a 1-methylquinolinium scaffold were synthesized. The inhibitors possess a variety of substituent groups including the cyclic or linear amine skeleton at the 2- and 4-position of the quinolinium ring for structure-activity relationship study. In general, the inhibitors bearing a cyclic amine substituent at the 4-position of the quinolinium ring showed better antibacterial activity (MIC down to 0.25 µg/mL) than that at the 2-position, especially against Gram-positive bacteria. Among the twenty FtsZ inhibitors examined in various assays, A3 was identified to exhibit excellent antibacterial activity against S. aureus (MIC = 0.5-1 µg/mL), S. epidermidis (MIC = 0.25 µg/mL) and E. faecium (MIC = 1-8 µg/mL). More importantly, A3 showed low hemolytic toxicity (IC5 = 64 µg/mL) and was found not readily to induce drug resistance. A3 at 2-8 µg/mL promoted the polymerization of FtsZ and interrupted the bacterial division. Furthermore, the ligand-FtsZ interaction study conducted with circular dichroism and molecular docking revealed that A3 induced secondary structure changes of FtsZ protein upon binding to the interdomain cleft of the protein. A3 is thus a potent inhibitor of FtsZ and shows potential to be used as a new antibacterial agent against drug-resistant bacteria.

From Mouth to Brain: Distinct Supragingival Plaque Microbiota Composition in Cerebral Palsy Children With Caries.

Children with cerebral palsy (CP) present a higher prevalence and severity of caries. Although researchers have studied multiple risk factors for caries in CP, the role of microorganisms in caries remains one of the critical factors worth exploring. In order to explore the differences in the supragingival plaque microbiota (SPM), supragingival plaque samples were collected from 55 CP children and 23 non-CP children for 16S rRNA sequencing. Distinct SPM composition was found between CP children with severe caries (CPCS) and non-CP children with severe caries (NCPCS). Further subanalysis was also done to identify if there were any differences in SPM among CP children with different degrees of caries, namely, caries-free (CPCF), mild to moderate caries (CPCM), and severe caries (CPCS). After selecting the top 15 most abundant species in all groups, we found that CPCS was significantly enriched for Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, Porphyromonas endodontalis, Catonella morbi, Alloprevotella tannerae, Parvimonas micra, Streptobacillus moniliformis, and Porphyromonas canoris compared to NCPCS. By comparing CPCF, CPCM, and CPCS, we found that the core caries-associated microbiota in CP children included Prevotella, Alloprevotella, Actinomyces, Catonella, and Streptobacillus, while Capnocytophaga and Campylobacter were dental health-associated microbiota in CP children. Alpha diversity analysis showed no significant difference between NCPCS and CPCS, but the latter had a much simpler core correlation network than that of NCPCS. Among CP children, CPCM and CPCF displayed lower bacterial diversity and simpler correlation networks than those of CPCS. In summary, the study showed the specific SPM characteristics of CPCS compared to NCPCS and revealed the core SPM in CP children with different severities of caries (CPCF, CPCM, and CPCS) and their correlation network. Hopefully, the study would shed light on better caries prevention and therapies for CP children. Findings from the current study offer exciting insights that warrant larger cohort studies inclusive of saliva and feces samples to investigate the potential pathogenic role of oral microbiota through the oral-gut-brain axis in CP children with caries.

Cosmeceutical Therapy: Engaging the Repercussions of UVR Photoaging on the Skin's Circadian Rhythm.

Sunlight is an important factor in regulating the central circadian rhythm, including the modulation of our sleep/wake cycles. Sunlight had also been discovered to have a prominent influence on our skin's circadian rhythm. Overexposure or prolonged exposure to the sun can cause skin photodamage, such as the formation of irregular pigmentation, collagen degradation, DNA damage, and even skin cancer. Hence, this review will be looking into the detrimental effects of sunlight on our skin, not only at the aspect of photoaging but also at its impact on the skin's circadian rhythm. The growing market trend of natural-product-based cosmeceuticals as also caused us to question their potential to modulate the skin's circadian rhythm. Questions about how the skin's circadian rhythm could counteract photodamage and how best to maximize its biopotential will be discussed in this article. These discoveries regarding the skin's circadian rhythm have opened up a completely new level of understanding of our skin's molecular mechanism and may very well aid cosmeceutical companies, in the near future, to develop better products that not only suppress photoaging but remain effective and relevant throughout the day.

Psychological Symptoms in COVID-19 Patients: Insights into Pathophysiology and Risk Factors of Long COVID-19.

There is growing evidence of studies associating COVID-19 survivors with increased mental health consequences. Mental health implications related to a COVID-19 infection include both acute and long-term consequences. Here we discuss COVID-19-associated psychiatric sequelae, particularly anxiety, depression, and post-traumatic stress disorder (PTSD), drawing parallels to past coronavirus outbreaks. A literature search was completed across three databases, using keywords to search for relevant articles. The cause may directly correlate to the infection through both direct and indirect mechanisms, but the underlying etiology appears more complex and multifactorial, involving environmental, psychological, and biological factors. Although most risk factors and prevalence rates vary across various studies, being of the female gender and having a history of psychiatric disorders seem consistent. Several studies will be presented, demonstrating COVID-19 survivors presenting higher rates of mental health consequences than the general population. The possible mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the brain, affecting the central nervous system (CNS) and causing these psychiatric sequelae, will be discussed, particularly concerning the SARS-CoV-2 entry via the angiotensin-converting enzyme 2 (ACE-2) receptors and the implications of the immune inflammatory signaling on neuropsychiatric disorders. Some possible therapeutic options will also be considered.

Biological insights into the piericidin family of microbial metabolites.

Extensively produced by members of the genus Streptomyces, piericidins are a large family of microbial metabolites, which consist of main skeleton of 4-pyridinol with methylated polyketide side chain. Nonetheless, these metabolites show differences in their bioactive potentials against micro-organisms, insects and tumour cells. Due to its close structural similarity with coenzyme Q, piericidins also possess an inhibitory activity against NADH dehydrogenase as well as Photosystem II. This review studied the latest research progress of piericidins, covering the chemical structure and physical properties of newly identified members, bioactivities, biosynthetic pathway with gene clusters and future prospect. With the increasing incidence of drug-resistant human pathogen strains and cancers, this review aimed to provide clues for the development of either new potential antibiotics or anti-tumour agents.

Bacterial extracellular vesicles in biofluids as potential diagnostic biomarkers.

INTRODUCTION: Extracellular vesicles (EVs) are spherical membrane-derived lipid bilayers released by cells. The human microbiota consists of trillions of microorganisms, with bacteria being the largest group secreting microbial EVs. The discovery of bacterial EVs (BEVs) has garnered interest among researchers as potential diagnostic markers, given that the microbiota is known to be associated with various diseases and EVs carry important macromolecular cargo for intercellular interaction. AREAS COVERED: The differential bacterial composition identified from BEVs isolated from biofluids between patients and healthy controls may be valuable for detecting diseases. Therefore, BEVs may serve as novel diagnostic markers. Literature search on PubMed and Google Scholar databases was conducted. In this special report, we outline the commonly used approach for investigating BEVs in biofluids, the 16S ribosomal RNA gene sequencing of V3-V4 hypervariable regions, and the recent studies exploring the potential of BEVs as biomarkers for various diseases. EXPERT OPINION: The emerging field of BEVs offers new possibilities for the diagnosis of various types of diseases, although there remain issues that need to be resolved in this research area to implement BEVs in clinical applications. Hence, it is important for future studies to take these challenges into consideration when investigating the diagnostic value of BEVs.

Finding a Balance in the Vaginal Microbiome: How Do We Treat and Prevent the Occurrence of Bacterial Vaginosis?

Bacterial vaginosis (BV) has been reported in one-third of women worldwide at different life stages, due to the complex balance in the ecology of the vaginal microbiota. It is a common cause of abnormal vaginal discharge and is associated with other health issues. Since the first description of anaerobic microbes associated with BV like Gardnerella vaginalis in the 1950s, researchers have stepped up the game by incorporating advanced molecular tools to monitor and evaluate the extent of dysbiosis within the vaginal microbiome, particularly on how specific microbial population changes compared to a healthy state. Moreover, treatment failure and BV recurrence rate remain high despite the standard antibiotic treatment. Consequently, researchers have been probing into alternative or adjunct treatments, including probiotics or even vaginal microbiota transplants, to ensure successful treatment outcomes and reduce the colonization by pathogenic microbes of the female reproductive tract. The current review summarizes the latest findings in probiotics use for BV and explores the potential of vaginal microbiota transplants in restoring vaginal health.

The Use of Fecal Microbiome Transplant in Treating Human Diseases: Too Early for Poop?

Fecal microbiome transplant (FMT) has gained popularity over the past few years, given its success in treating several gastrointestinal diseases. At the same time, microbial populations in the gut have been shown to have more physiological effects than we expected as "habitants" of the gut. The imbalance in the gut microbiome or dysbiosis, particularly when there are excessive harmful pathogens, can trigger not just infections but can also result in the development of common diseases, such as cancer and cardiometabolic diseases. By using FMT technology, the dysbiosis of the gut microbiome in patients can be resolved by administering fecal materials from a healthy donor. The current review summarizes the history and current uses of FMT before suggesting potential ideas for its high-quality application in clinical settings.

COVID-19: Insights into Potential Vaccines.

People around the world ushered in the new year 2021 with a fear of COVID-19, as family members have lost their loved ones to the disease. Millions of people have been infected, and the livelihood of many has been jeopardized due to the pandemic. Pharmaceutical companies are racing against time to develop an effective vaccine to protect against COVID-19. Researchers have developed various types of candidate vaccines with the release of the genetic sequence of the SARS-CoV-2 virus in January. These include inactivated viral vaccines, protein subunit vaccines, mRNA vaccines, and recombinant viral vector vaccines. To date, several vaccines have been authorized for emergency use and they have been administered in countries across the globe. Meanwhile, there are also vaccine candidates in Phase III clinical trials awaiting results and approval from authorities. These candidates have shown positive results in the previous stages of the trials, whereby they could induce an immune response with minimal side effects in the participants. This review aims to discuss the different vaccine platforms and the clinical trials of the candidate vaccines.

Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice.

Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of A. muciniphila abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD.IMPORTANCE Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.

Streptomyces sp. Strain MUSC 125 from Mangrove Soil in Malaysia with Anti-MRSA, Anti-Biofilm and Antioxidant Activities.

There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase (pks) gene clusters, pksI and pksII, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.

Comparative efficacy of antibiotic(s) alone or in combination of corticosteroids in adults with acute bacterial meningitis: A systematic review and network meta-analysis.

OBJECTIVE: To compare relative efficacy of different antibiotic therapies either with or without the addition of corticosteroids among adult patients with acute bacterial meningitis on all-cause mortality, neurological complications and any hearing loss. METHODS: We searched nine databases from inception to 8 February 2018 for randomized controlled trials evaluating pharmacological interventions and clinical outcomes in adult bacterial meningitis. An updated search from 9 February to 9 March 2020 was performed, and no new studies met the inclusion criteria. Study quality was assessed using the revised Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system was used for quality of evidences evaluation. Meta-analyses were conducted to estimate the risk ratio with 95% confidence interval for both direct and indirect comparisons on the primary outcomes of all-cause mortality, neurologic sequelae and any hearing loss. The study was registered in PROSPERO (CRD42018108062). RESULTS: Nine RCTs were included in systematic review, involving 1,002 participants with a mean age ranging between 25.3 to 50.56 years. Six RCTs were finally included in the network-meta analysis. No significant difference between treatment was noted in meta-analysis. Network meta-analysis suggests that corticosteroids in combination with antibiotic therapy was more effective in reducing the risk of any hearing loss compared to mono antibiotic therapy (RR 0.64; 95%CI, 0.45 to 0.91, 4 RCTs, moderate certainty of evidence). Numerical lower risk of mortality and neurological complications was also shown for adjunctive corticosteroids in combination with antibiotic therapy versus mono antibiotic therapy (RR 0.65; 95%CI, 0.42 to 1.02, 6 RCTs, moderate certainty of evidence; RR 0.75; 95%CI, 0.47 to 1.18, 6 RCTs, moderate certainty of evidence). No differences were noted in the adverse events between different therapies. The overall certainty of evidence was moderate to very low for all primary outcomes examined. CONCLUSIONS: Results of this study suggest that corticosteroids therapy in combination with antibiotic is more effective than mono antibiotic therapy in reducing the risk of any hearing loss in adult patients with acute bacterial meningitis. More well-design RCTs to investigate relative effective treatments in acute bacterial meningitis particularly in adult population should be mandated to aid clinicians in treatment recommendations.