Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIMS: Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. METHODS: We conducted a systematic review, meta-analysis, and meta-regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random-effects meta-analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. RESULTS: Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (-9.97 mg/dL [95% CI: -15.08; -4.87], p < 0.0001), low-density lipoprotein (-6.29 mg/dL [95% CI: -9.25; -3.33], p < 0.0001), high-density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very-low-density lipoprotein (-4.52 mg/dL [95% CI: -6.36; -2.67], p < 0.0001) and triglyceride (-22.93 mg/dL [95% CI: -33.99; -11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. CONCLUSIONS: Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter-study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.

Severity of the Omicron SARS-CoV-2 variant compared with the previous lineages: A systematic review.

The Omicron variant was first detected in October 2021, which evolved from the original SARS-CoV-2 strain and was found to possess many mutations. Immune evasion was one of the notable consequences of these mutations. Despite Omicron exhibiting increased transmissibility, the rates of hospitalizations and deaths among patients infected with this variant were substantially lower when compared to other strains. However, concluding that the Omicron variant is less severe than other variants of SARS-CoV-2 requires consideration of multiple factors, including the vaccination status of infected patients as well as any previous infections with other variants. This review compiled data about any reported indicators of severity in Omicron-infected patients, including studies comparing Omicron with other variants while adjusting for confounders. A comprehensive search was conducted using different databases to target any studies about Omicron. In total, 62 studies met our inclusion criteria and were included in this study. Many studies reported a significantly reduced risk of hospitalization, ICU admission, need for oxygenation/ventilation, and death in Omicron-infected patients compared to patients infected with other variants, such as Delta. Some studies, however, reported comparable severity in Omicron infected patients as to other variants emphasizing a substantial risk for severe illness. Furthermore, the COVID-19 vaccines were less effective against Omicron relative to previous lineages, except after receiving the booster dose. One study recommended vaccination during pregnancy, which may help prevent future cases of severe SARS-CoV-2 pneumonia in neonates and young infants due to the transfer of humoral response from the mother.

Role of previous infection with SARS-CoV-2 in protecting against omicron reinfections and severe complications of COVID-19 compared to pre-omicron variants: a systematic review.

BACKGROUND: The SARS-CoV-2 virus elicited a major public concern worldwide since December 2019 due to the high number of infections and deaths caused by COVID-19. The Omicron variant was detected in October 2021 which evolved from the wild-type SARS-CoV-2 and was found to possess many mutations. Omicron exhibited high transmissibility and immune evasion as well as reduced severity when compared to the earlier variants. Although vaccinated individuals were largely protected against infections in previous waves, the high prevalence of both reinfections and breakthrough infections with Omicron was observed. The aim of this review is to understand the effectiveness of previous infection on subsequent reinfection, given its significance in driving public health policy, including vaccination prioritization and lockdown requirements. METHODS: A comprehensive literature search was conducted using several databases to target studies reporting data related to the effectiveness of the previous infection with SARS-CoV-2 in protecting against the Omicron variant. Screening of the studies, quality assessment and data extraction were conducted by two reviewers for each study. RESULTS: Only 27 studies met our inclusion criteria. It was observed that previous infection was less effective in preventing reinfections with the Omicron variant compared to the Delta variant irrespective of vaccination status. Furthermore, being fully vaccinated with a booster dose provided additional protection from the Omicron variant. Additionally, most infections caused by Omicron were asymptomatic or mild and rarely resulted in hospitalizations or death in comparison to the Delta wave. CONCLUSION: A majority of the studies reached a consensus that although previous infection provides some degree of immunity against Omicron reinfection, it is much lower in comparison to Delta. Full vaccination with two doses was more protective against Delta than Omicron. Receiving a booster dose provided additional protection against Omicron. It is therefore clear that neither vaccination nor previous infection alone provide optimal protection; hybrid immunity has shown the best results in terms of protecting against either Omicron or Delta variants. However, additional research is needed to quantify how long immunity from vaccination versus previous infection lasts and whether individuals will benefit from variant-specific vaccinations to enhance protection from infection.

Cardiovascular and haematological events post COVID-19 vaccination: A systematic review.

Since COVID-19 took a strong hold around the globe causing considerable morbidity and mortality, a lot of effort was dedicated to manufacturing effective vaccines against SARS-CoV-2. Many questions have since been raised surrounding the safety of the vaccines, and a lot of media attention to certain side effects. This caused a state of vaccine hesitancy that may prove problematic in the global effort to control the virus. This review was undertaken with the aim of putting together all the reported cardiovascular and haematological events post COVID-19 vaccination in published literature and to suggest possible mechanisms to explain these rare phenomena.

Lymphadenopathy post-COVID-19 vaccination with increased FDG uptake may be falsely attributed to oncological disorders: A systematic review.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic that continues to cause numerous deaths to date. Four vaccines have been approved by the Food and Drug Administration as of July 2021 to prevent the transmission of COVID-19: Pfizer, Moderna, AstraZeneca, and Janssen. These vaccines have shown great efficacy and safety profile. One side effect that has been widely reported is post-COVID-19 vaccination lymphadenopathy. Due to the mimicry of the lymphadenopathy for metastases in some oncologic patients, there have been reports of patients who underwent biopsies that showed pathologic confirmation of benign reactive lymphadenopathy secondary to the COVID-19 vaccine. Therefore, understanding the incidence of lymphadenopathy post-COVID-19 vaccinations will help guide radiologists and oncologists in their management of patients, both present oncologic patients, and patients with concerns over their newly presenting lymphadenopathy. A systematic literature search was performed using several databases to identify relevant studies that reported lymphadenopathy post-COVID-19 vaccination. Our results revealed that several cases have been detected in patients undergoing follow-up fluorodeoxyglucose (FDG)-positron emission tomography-computerized tomography scans where lymph nodes ipsilateral to the vaccine injection site show increased uptake of FDG. Thus, knowledge of the incidence of lymphadenopathy may help avoid unnecessary biopsies, interventions, and changes in management for patients, especially oncologic patients who are at risk for malignancies.

The effect of microbiome-modulating probiotics, prebiotics and synbiotics on glucose homeostasis in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIM/HYPOTHESIS: The globally escalating diabetes epidemic is responsible for significant morbidity and mortality. Microbiome-modulating nutraceuticals have been investigated for their potential to restore metabolic and floral homeostasis in type 2 diabetic patients METHODS: A systematic review, meta-analyses and meta-regressions were conducted to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of glucose homeostasis based on a multi-database search of clinical trials published through April 10, 2022. Data was pooled using random effects meta-analyses and reported as mean differences with 95% confidence intervals (CIs), followed by univariate linear model meta-regression. RESULTS: Data from 68 trial comparisons across 58 studies (n = 3835) revealed that, compared to placebo/control group, administration of pro/pre/synbiotics was associated with statistically significant changes in fasting plasma glucose (-12.41 mg/dl [95% CI: -15.94; -8.88], p 0.0001), glycated hemoglobin (-0.38% [95% CI: -0.47; -0.30], p 0.0001), fasting insulin (-1.49 µU/mL [95% CI: -2.12; -0.86], p 0.0001), HOMA-IR (-0.69 [95% CI: -1.16; -0.23], p = 0.0031) and QUICKI (0.0148 [95% CI: 0.0052; 0.0244], p = 0.0025), but not C-peptide (-0.0144 ng/mL [95% CI: -0.2564; -0.2275], p = 0.9069). Age, baseline BMI, baseline biomarker value, pro/prebiotic dosage, trial duration, nutraceutical type, and recruitment region significantly affected the potential of pro/pre/synbiotics use as personalized diabetes adjunct therapy. Lastly, we discuss unexplained observations and directives for future trials, with the aim of maximizing our understanding of how microbiome-modulating nutraceuticals can treat various metabolic diseases CONCLUSIONS: Pro/pre/synbiotic supplementation improved glucose homeostasis in diabetic patients. Our results support their potential use as adjunct therapy for improving glycemia and insulinemia alongside pharmacological therapeutics.

Renal Health Improvement in Diabetes through Microbiome Modulation of the Gut-Kidney Axis with Biotics: A Systematic and Narrative Review of Randomized Controlled Trials.

Diabetes mellitus is the most common endocrine disorder worldwide, with over 20% of patients ultimately developing diabetic kidney disease (DKD), a complex nephropathic complication that is a leading cause of end-stage renal disease. Various clinical trials have utilized probiotics, prebiotics, and synbiotics to attempt to positively modulate the gut microbiome via the gut-kidney axis, but consensus is limited. We conducted a multi-database systematic review to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of renal health in diabetes, based on studies published through 10 April 2022. Adhering to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, relevant articles were systematically screened and extracted by independent reviewers; subsequently, results were systematically compiled, analyzed, and expanded through a narrative discussion. A total of 16 publications encompassing 903 diabetic individuals met the inclusion criteria. Our findings show that some studies report statistically significant changes in common renal markers, such as serum creatinine, estimated glomerular filtration rate, blood urea nitrogen/urea, microalbuminuria, and uric acid, but not on serum albumin, sodium, potassium, phosphorous, or total urine protein. Interestingly, these nutraceuticals seem to increase serum uric acid concentrations, an inflammatory marker usually associated with decreased renal health. We found that probiotics from the Lactobacillus and Bifidobacterium families were the most investigated, followed by Streptococcus thermophilus. Prebiotics including inulin, galacto-oligosaccharide, and resistant dextrin were also examined. The single-species probiotic soymilk formulation of Lactobacillus plantarum A7 possessed effects on multiple renal biomarkers in DKD patients without adverse events. We further investigated the optimum nutraceutical formulation, discussed findings from prior studies, described the gut-kidney axis in diabetes and DKD, and finally commented on some possible mechanisms of action of these nutraceuticals on renal health in diabetics. Although probiotics, prebiotics, and synbiotics have shown some potential in ameliorating renal health degradation in diabetes via gut-kidney axis crosstalk, larger and more convincing trials with focused objectives and next-generation nutraceutical formulations are required to investigate their possible role as adjunct therapy in such patients.

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review.

The ongoing COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a globally leading public health concern over the past two years. Despite the development and administration of multiple vaccines, the mutation of newer strains and challenges to universal immunity has shifted the focus to the lack of efficacious drugs for therapeutic intervention for the disease. As with SARS-CoV, MERS-CoV, and other non-respiratory viruses, flavonoids present themselves as a promising therapeutic intervention given their success in silico, in vitro, in vivo, and more recently, in clinical studies. This review focuses on data from in vitro studies analyzing the effects of flavonoids on various key SARS-CoV-2 targets and presents an analysis of the structure-activity relationships for the same. From 27 primary papers, over 69 flavonoids were investigated for their activities against various SARS-CoV-2 targets, ranging from the promising 3C-like protease (3CLpro) to the less explored nucleocapsid (N) protein; the most promising were quercetin and myricetin derivatives, baicalein, baicalin, EGCG, and tannic acid. We further review promising in silico studies featuring activities of flavonoids against SARS-CoV-2 and list ongoing clinical studies involving the therapeutic potential of flavonoid-rich extracts in combination with synthetic drugs or other polyphenols and suggest prospects for the future of flavonoids against SARS-CoV-2.

A cord of four strands: Perspective of pre-medical and medical students on combined teaching modalities in undergraduate biochemistry.

Despite being a traditional coursework for pre-medical and medical students around the globe, biochemistry education suffers from a lack of positive appreciation due to the nature of the subject combined with deficiency of teaching modalities. A first semester biochemistry course was designed to include four different teaching modalities: lectures, recitations, case studies, and student presentations. A multi-item, anonymous, and voluntary questionnaire was distributed to students who had just completed the course and to those who had taken it the previous year. The questionnaire asked students to evaluate the course and how the different modalities affected their learning. These questionnaires took place in a two-year period between 2020 and 2021. Eighty-six (46%) of 186 total students responded. The vast majority of respondents agreed with the use of multimodal teaching techniques with respect to its impact on overall preparedness for future coursework, understanding, and enjoyability. Lectures and recitations were found to be the most useful in information retention and learning, although the same were found to be less enjoyable than other modalities. Although case studies and presentations were found to be enjoyable, most students ranked them low in terms of information retention and were the most voted to be removed from the course. There was general agreement between premedical and medical students' perception on the usefulness of the multimodal teaching techniques with respect to medical biochemistry modules and standardized exams. The agreement between cohorts suggests the premedical students accurately evaluated the usefulness of the course for the following year and validates the usefulness of the premedical student surveys. Use of multiple modalities in biochemistry education can be of substantial benefit in engaging and preparing students for further education.

Experimental and computational investigation of the effect of Hsc70 structural variants on inhibiting amylin aggregation.

The misfolding and aggregation of human islet amyloid polypeptide (hIAPP), also known as amylin, have been implicated in the pathogenesis of type 2 diabetes (T2D). Heat shock proteins, specifically, heat shock cognate 70 (Hsc70), are molecular chaperones that protect against hIAPP misfolding and inhibits its aggregation. Nevertheless, there is an incomplete understanding of the mechanistic interactions between Hsc70 domains and hIAPP, thus limiting their potential therapeutic role in diabetes. This study investigates the inhibitory capacities of different Hsc70 variants, aiming to identify the structural determinants that strike a balance between efficacy and cytotoxicity. Our experimental findings demonstrate that the ATPase activity of Hsc70 is not a pivotal factor for inhibiting hIAPP misfolding. We underscore the significance of the C-terminal substrate-binding domain of Hsc70 in inhibiting hIAPP aggregation, emphasizing that the removal of the lid subdomain diminishes the inhibitory effect of Hsc70. Additionally, we employed atomistic discrete molecular dynamics simulations to gain deeper insights into the interaction between Hsc70 variants and hIAPP. Integrating both experimental and computational findings, we propose a mechanism by which Hsc70's interaction with hIAPP monomers disrupts protein-protein connections, primarily by shielding the ß-sheet edges of the Hsc70-ß-sandwich. The distinctive conformational dynamics of the alpha helices of Hsc70 potentially enhance hIAPP binding by obstructing the exposed edges of the ß-sandwich, particularly at the ß5-ß8 region along the alpha helix interface. This, in turn, inhibits fibril growth, and similar results were observed following hIAPP dimerization. Overall, this study elucidates the structural intricacies of Hsc70 crucial for impeding hIAPP aggregation, improving our understanding of the potential anti-aggregative properties of molecular chaperones in diabetes treatment.

The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review.

AIMS: Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes. MATERIALS AND METHODS: We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19. KEY FINDINGS: The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0 % to 11 % in the intervention groups, as compared to 3 % to 30 % in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders. SIGNIFICANCE: The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.

Alcohol and Atrial Fibrillation: A Pathophysiologic Perspective.

Atrial fibrillation (AF) is the most common cardiac arrhythmia responsible for significant morbidity and mortality. Its burden on patients and the health care system is only expected to increase. Several studies have established a dose-response relationship between the amount and frequency of alcohol consumption and the incidence of new onset AF independent of sex, age, and other risk factors. This causal relationship is mediated by the impact alcohol consumption has on conduction properties of the atrium, structural and cellular effect on cardiac myocytes, and dysregulation of the autonomic nervous system. This article reviews the current literature supporting the link between alcohol consumption and AF while attempting to provide an insight into pathophysiological mechanisms.

An investigation into the potential action of polyphenols against human Islet Amyloid Polypeptide aggregation in type 2 diabetes.

Type 2 diabetes (T2D), a chronic metabolic disease characterized by hyperglycemia, results in significant disease burden and financial costs globally. Whilst the majority of T2D cases seem to have a genetic basis, non-genetic modifiable and non-modifiable risk factors for T2D include obesity, diet, physical activity and lifestyle, smoking, age, ethnicity, and mental stress. In healthy individuals, insulin secretion from pancreatic islet ß-cells is responsible for keeping blood glucose levels within normal ranges. T2D patients suffer from multifactorial onset of ß-cell dysfunction and/or loss of ß-cell mass owing to reactive oxygen species (ROS) production, mitochondrial dysfunction, autophagy, and endoplasmic reticulum (ER) stress. Most predominantly however, and the focus of this review, it is the aggregation and misfolding of human Islet Amyloid Polypeptide (hIAPP, also known as amylin), which is detrimental to ß-cell function and health. Whilst hIAPP is found in healthy individuals, its misfolded version is cytotoxic and able to induce ß-cell dysfunction and/or death through various mechanisms including membrane changes in ß-cell causing influx of calcium ions, arresting complete granule membrane recovery and ER stress. There are several existing therapeutics for T2D. However, there is a need for alternative or adjunct therapies for T2D with milder adverse effects and greater availability. Foremost among the potential natural therapeutics are polyphenols. Extensive data from studies evaluating the potential of polyphenols to inhibit hIAPP aggregation and disassemble aggregated hIAPP are promising. Moreover, in-vivo, and in-silico studies also highlight the potential effects of polyphenols against hIAPP aggregation and mitigation of larger pathological effects of T2D. Whilst there have been some promising clinical studies on the therapeutic potential of polyphenols, extensive further clinical studies and in-vitro studies evaluating the mechanisms of action and ideal doses for many of these compounds are required. The need for these studies is made more important by the postulated link between Alzheimer's disease (AD) and T2D pathophysiology given the similar aggregation process of their respective amyloid proteins, which evokes thoughts of cross-reactive polyphenols which can be effective for both AD and T2D patients.

Evaluating the inhibitory potential of natural compound luteolin on human lysozyme fibrillation.

Numerous pathophysiological conditions known as amyloidosis, have been connected to protein misfolding leading to aggregation of proteins. Inhibition of cytotoxic aggregates or disaggregation of the preformed fibrils is thus one of the important strategies in the prevention of such diseases. Growing interest and exploration of identification of small molecules mainly natural compounds can prevent or delay amyloid fibril formation. We examined the mechanism of interaction and inhibition of human lysozyme (HL) aggregates with luteolin (LT). Biophysical and computational approaches have been employed to study the effect of LT on HL amyloid aggregation. Transmission Electronic Microscopy, Thioflavin T fluorescence, UV-vis spectroscopy, and RLS demonstrates that LT inhibit HL fibril formation. ANS fluorescence and hemolytic assay was also employed to examine the effect of the LT on toxicity of HL aggregation. Docking and molecular dynamics results showed that LT interacted with HL via hydrophobic and hydrogen interactions, thus reducing fibrillation levels. These findings highlight the benefit of polyphenols as safe therapy for preventing amyloid related diseases.

Deep Brain Stimulation beyond the Clinic: Navigating the Future of Parkinson's and Alzheimer's Disease Therapy.

Deep brain stimulation (DBS) is a surgical procedure that uses electrical neuromodulation to target specific regions of the brain, showing potential in the treatment of neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). Despite similarities in disease pathology, DBS is currently only approved for use in PD patients, with limited literature on its effectiveness in AD. While DBS has shown promise in ameliorating brain circuits in PD, further research is needed to determine the optimal parameters for DBS and address any potential side effects. This review emphasizes the need for foundational and clinical research on DBS in different brain regions to treat AD and recommends the development of a classification system for adverse effects. Furthermore, this review suggests the use of either a low-frequency system (LFS) or high-frequency system (HFS) depending on the specific symptoms of the patient for both PD and AD.

Knowledge, Awareness, and Attitude of Healthcare Stakeholders on Alzheimer's Disease and Dementia in Qatar.

Dementia is characterized by progressive cognitive decline, memory impairment, and disability. Alzheimer's disease (AD) accounts for 60-70% of cases, followed by vascular and mixed dementia. Qatar and the Middle East are at increased risk owing to aging populations and high prevalence of vascular risk factors. Appropriate levels of knowledge, attitudes, and awareness amongst health care professionals (HCPs) are the need of the hour, but literature indicates that these proficiencies may be inadequate, outdated, or markedly heterogenous. In addition to a review of published quantitative surveys investigating similar questions in the Middle East, a pilot cross-sectional online needs-assessment survey was undertaken to gauge these parameters of dementia and AD among healthcare stakeholders in Qatar between 19 April and 16 May 2022. Overall, 229 responses were recorded between physicians (21%), nurses (21%), and medical students (25%), with two-thirds from Qatar. Over half the respondents reported that >10% of their patients were elderly (>60 years). Over 25% reported having contact with >50 patients with dementia or neurodegenerative disease annually. Over 70% had not undertake related education/training in the last 2 years. The knowledge of HCPs regarding dementia and AD was moderate (mean score of 5.3 ± 1.5 out of 7) and their awareness of recent advances in basic disease pathophysiology was lacking. Differences existed across professions and location of respondents. Our findings lay the groundwork for a call-to-action for healthcare institutions to improve dementia care within Qatar and the Middle East region.

Effectiveness of the pre-Omicron COVID-19 vaccines against Omicron in reducing infection, hospitalization, severity, and mortality compared to Delta and other variants: A systematic review.

Despite widespread mass rollout programs, the rapid spread of the SARS-CoV-2 Omicron variant called into question the effectiveness of the existing vaccines against infection, hospitalization, severity, and mortality compared to previous variants. This systematic review summarizes and compares the effectiveness of the COVID-19 vaccines, with respect to the above outcomes in adults, children, and adolescents. A comprehensive literature search was undertaken on several databases. Only 51 studies met our inclusion criteria, revealing that the protection from primary vaccination against Omicron infection is inferior to protection against Delta and Alpha infections and wanes faster over time. However, mRNA vaccine boosters were reported to reestablish effectiveness, although to a lower extent against Omicron. Nonetheless, primary vaccination was shown to preserve strong protection against Omicron-associated hospitalization, severity, and death, even months after last dose. However, boosters provide more robust and longer-lasting protection against hospitalizations due to Omicron as compared to only primary series.

Can probiotic, prebiotic, and synbiotic supplementation modulate the gut-liver axis in type 2 diabetes? A narrative and systematic review of clinical trials.

Background: Type 2 diabetes, one of the most common noncommunicable diseases, is a metabolic disorder that results in failed homeostatic control in several body systems, including hepatic function. Due to the gut microbiome's potential role in diabetes' pathogenesis, prebiotics, probiotics, and synbiotics have been proposed as complimentary therapeutic approaches aimed at microbiota readjustment. Methods: A systematic review was conducted on PubMed, Scopus, Web of Science, Embase, and the Cochrane Library examining the effect of probiotics, prebiotics, and synbiotics on hepatic biomarkers in patients with diabetes. Results: From 9,502 search hits, 10 studies met the inclusion criteria and were included in this review. A total of 816 participants (460 intervention and 356 control) were investigated for the effects of nine different hepatic biomarker measurements including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, bilirubin, liver steatosis, liver stiffness, fatty liver index, and gamma-glutamyl transferase levels. Of the 13 intervention groups analyzed from the 10 studies, 3 were prebiotic interventions, 3 were single species probiotic interventions, 3 were multi-species probiotic interventions, and 4 were synbiotic interventions. Nutraceuticals used in these trials included six genera of bacteria (Lactobacillus, Bifidobacterium, Streptococcus, Acetobacter, Lactococcus, and Propionibacterium), five different prebiotic formulations (inulin, inulin and beta carotene, chicory inulin enriched with oligofructose, galacto-oligosaccharides syrup, and powdered cinnamon), or a combination of these to form multi-species probiotics or synbiotics. Conclusion: Although some studies showed insignificant changes in hepatic biomarkers, generally the results yielded a decrease in liver damage due to reduced oxidative stress, pro-inflammatory cytokines, gut dysbiosis, and insulin resistance which led to improvements in hepatic biomarker levels.

The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review.

Background: One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods: Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results: From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion: Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.