The Effect of Fecal Microbiota Transplantation on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis.

PURPOSE: Cardiometabolic disease (CMD) is increasing along with its predisposing factors and adverse consequences. As gut microbiota dysbiosis is established in these patients, fecal microbiota transplantation (FMT), which alters the bacterial composition of the intestine, supposedly can help improve cardiometabolic disturbances. We conducted a systematic review and meta-analysis evaluating the impact of FMT on the cardiometabolic parameters and gut microbiota composition of patients experiencing at least one cardiometabolic issue. METHODS: Eligible studies were searched through the PubMed, Web of Science, and Scopus databases until December 2022. The initial search results underwent duplication removal and screening until each included study was scanned for intended data. The Cochrane risk of bias tool was used to evaluate the methodologic accuracy of studies and the random effects model was used for conducting the meta-analysis. FINDINGS: Eighteen of the original 2414 articles from the literature search were entered into the systematic review; of these, 11 were included in the meta-analysis. Insulin showed a significant decrease by 24.7 pmol/L (weighted mean difference [WMD], -24.77; 95% CI, -48.704 to -0.848) after short-term follow-up, and HDL increased by 0.1 mmol/l(WMD, 0.106; 95% CI, 0.027 to 0.184) and 0.12 mmol/l(WMD, 0.120; 95% CI, 0.003 to 0.237) in those using a capsule deliver mode and in short-term follow-up, respectively. No significant changes were seen in other lipid profiles, blood glucose, insulin resistance, or anthropometric indices. In addition, multiple studies reported gut microbiota alterations after the intervention, including an increase in butyrate-producing species. IMPLICATIONS: Although some articles reported the beneficial effects of FMT on metabolic parameters, we failed to find a clinically significant alteration. Also, information regarding proper donors and the best method to induce FMT have not yet been sufficiently investigated, which should be considered along with means to prevent potential damages. PROSPERO identifier: CRD42022380705.

General and abdominal obesity trends in the Iranian adult population from 2004 to 2021.

Purpose: The prevalence of overweight/obesity and abdominal obesity is increasing worldwide, accompanied by an increase in the incidence of non-communicable diseases. This study aims to determine the trends of Body Mass Index (BMI) and prevalence of overweight/obesity and abdominal obesity changes in Iranian adult population from 2004 to 2021. Methods: We conducted this study based on the eight national surveys of noncommunicable disease risk factor surveillance (STEPS) from 2004 to 2021 in Iran. We estimated the crude and standardized mean of BMI and prevalence of general and abdominal obesity in these eight STEPS surveys data. Data weighted using post-stratification method and the trends depicted based on the standardized estimates. Results: Between 2004 and 2021, and based on the standardized estimates, the mean of BMI increased from 25.19 kg/m2 in 2004 to 26.63 kg/m2 in 2021 (P-value for trend = 0.03). The standardized mean of WC increased from 86.38 cm in 2004 to 91.65 cm in 2021 (P-value for trend = 0.38). The standardized prevalence of obesity (class I and II) increased from 14.54% in 2004 to 20.17% in 2021 (P-value for trend = 0.01). The standardized prevalence of obesity class III increased from 0.82% in 2004 to 1.35% in 2021 (P-value for trend = 0.03). The standardized prevalence of abdominal obesity based on the national and international cut-points increased, but the trend was not statistically significant [(National cut-point: 27.53% in 2004 to 40.43% in 2021 (P-value for trend = 0.71)) (International cut-point: 27.58% in 2004 to 41.81% in 2021 (P-value for trend = 0.06))]. Conclusion: The standardized mean of BMI and prevalence of overweight/obesity and abdominal obesity increased among Iranian adults between 2004 and 2021. Because of the negative public and clinical health implications of obesity, health policymakers should develop comprehensive programs to control this increasing trend of weight gain.

Evaluating the effectiveness of melatonin in reducing the risk of foot ulcers in diabetic patients.

Objectives: Diabetes and its complications, as a major health concern, are associated with morbidity and mortality around the world. One of these complications is diabetic foot ulcer. Factors such as hyperglycemia, neuropathy, vascular damage and impaired immune system can cause foot ulcers. The present review aims to study the potential effects of melatonin, the main product of pineal glands, on diabetic foot ulcers. Methods: A narrative review was performed using present literature in an attempt to identify the different aspects of melatonin's impact on diabetic foot ulcers by searching related keywords in electronic databases without any restriction. Results: This review shows that, melatonin has anti-diabetic effects. It is effective in reducing the risk of hyperglycemia, neuropathy, vascular damage and immune system impairment in diabetic patients. By reducing these complications with melatonin, correspondingly, the incidence of diabetic foot ulcers may also decrease in these patients. Conclusions: The results of this study indicate promising properties of melatonin while dealing with diabetic foot ulcers and their common underlying conditions, but still, it needs to be investigated more in future studies.

Trimethylamine N-Oxide as a Potential Risk Factor for Non-communicable Diseases: A Systematic Review.

BACKGROUND: Trimethylamine N-Oxide (TMAO), as a gut microbiota-derived metabolite, has been associated with a number of chronic diseases like cardiovascular diseases. OBJECTIVE: Considering the increasing prevalence of non-communicable diseases (NCDs), we conducted a systematic review to discuss the TMAO association with NCDs. METHODS: A comprehensive search has been conducted on PubMed, Web of Science, and Scopus databases up to December, 2020. The inclusion criteria were all related observational studies that surveyed the association between TMAO levels and non-communicable diseases. Interventional studies, animal experiments, reviews, case reports, letters, congress abstracts, and studies that were not published in English were excluded. Moreover, related review studies were separately discussed. RESULTS: Within 2191 recorded studies, 99 cross-sectional, case-control and cohort studies met the inclusion criteria. The most common diseases associated with TMAO levels are cardiovascular diseases, diabetes, kidney disease, stroke, inflammatory diseases, neurological disorders, and cancer. Elevated TMAO levels as a consequence of alteration in gut microbiota composition and dietary intake can lead to the incidence of NCDs. The high levels of TMAO can disrupt the homeostasis of glucose and lipids and induce inflammation that leads to serious NCDs. CONCLUSION: There is a dose-response relationship between TMAO levels and NCDs progression. Therefore, it can be studied as a therapeutic target or prognostic biomarker for dealing with NCDs.

Association of fat mass and obesity-associated (FTO) gene polymorphisms with non-communicable diseases (NCDs) in the Iranian population: A systematic review of observational studies.

Background: Single nucleotide polymorphisms have been implicated in various diseases, most notably non-communicable diseases (NCDs). The aim of this study was to review available evidence regarding associations between FTO polymorphisms and NCDs in the Iranian population. Methods: A comprehensive search was conducted through PubMed/Medline and Scopus databases up to December 2021, as well as reference lists of pertinent articles and key journals. All observational studies that examined the association between FTO gene polymorphisms and NCDs in the Iranian population were included. There was no limitation on the publication year. The Newcastle-Ottawa Scale (NOS) was used to assess the study's quality. Results: The initial search yielded 95 studies, of which 30 studies were included in the current systematic review. The underlying disorders were obesity, type 2 diabetes, breast and colorectal cancers, depression, and metabolic syndrome. These studies found an association between FTO gene polymorphisms and obesity in the Iranian population, but the relationship with other NCDs was debatable. Even though, other diseases such as diabetes and metabolic syndrome, which are closely related to obesity, may also be associated with FTO gene polymorphisms. Conclusion: FTO gene polymorphism appears to play a role in the occurrence of NCDs. Some of the study results may be misleading due to ethnic differences and the effect of other genetic factors on disease onset, which needs to be investigated further. Finally, FTO gene polymorphisms can be studied as a preventive or therapeutic target. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01139-4.

Effect of garlic extract on weight loss and gut microbiota composition in obese women: A double-blind randomized controlled trial.

Objective: From a nutritional perspective, garlic extract could be a prebiotic product, which is useful for obese subjects, and one of its health-promoting underlying mechanisms is modulating gut microbiota composition. In this randomized double-blind clinical trial, the goal was to determine the effect of Allium (garlic extract) on anthropometric indices and gut microbiota composition in obese women following a low-calorie diet. Materials and methods: Forty-three obese women were randomly divided into garlic extract (400 mg Allium sativum powder containing 1,100 mcg allicin/tablet) or placebo groups. During the 2 months of the study, each participant took two tablets per day. At the beginning and at the end of the clinical trial, anthropometric measurements were done and blood and fecal samples were collected. We evaluated the gut microbiota composition using quantitative real-time PCR. Results: In total, 16 subjects in each group completed the 2-month trial. Allium and placebo groups' participants had mean ages of 37.8 ± 7.4 and 34.2 ± 6.8 years, respectively (P > 0.05). Baseline body mass index (BMI) was significantly different between groups, subjects in the placebo group had lower BMI compared with the Allium group (P < 0.05). Allium and placebo caused a 1.7% and 2.7% decrease in BMI from the baseline values, respectively (P < 0.01). Fasting insulin level significantly decreased in the both groups (P < 0.01). Level of homeostasis model assessment of insulin resistance (HOMA-IR) has decreased significantly in the Allium group (P = 0.007). The frequency of Akkermansia had decreasing trend while the abundance of Faecalibacterium and Bifidobacterium showed increasing trend in the Allium group. Conclusion: In the both groups, a decrease in BMI and other anthropometric indices has been observed. Despite weight loss after following a low-calorie diet and taking Allium, slight changes have been shown in the composition of gut microbiota in obese women. Trial registration: This trial was registered in the Iranian Registry of Clinical Trials (IRCT) (code: IRCT090420001825N2).

Do patients with diabetic foot ulcer need booster dose of tetanus vaccine?

Purpose: Diabetic foot ulcer is a public health concern around the world. These wounds are prone to a variety of infections including Clostridium Tetani that may lead to tetanus. The aim of this study was to evaluate the immunity status as a result of tetanus vaccination and other preventive measures in these patients. Methods: We conducted a narrative review of previous studies which were related to the risk of tetanus infection in diabetic foot patients by searching electronic databases. Results: It was found that usually tetanus antibody titers in diabetic patients are below the protective level and they are not appropriately vaccinated. Therefore, diabetes and lack of immunity, put diabetic foot ulcer patients more at risk of tetanus. But this problem is not given serious attention in diabetes care. Conclusions: Thus, it is recommended to provide specific guidelines for tetanus vaccination and prophylaxis in diabetic patients. These recommendations can play a vital role in the prevention of diabetic foot ulcers complication.

Assessment of fecal Akkermansia muciniphila in patients with osteoporosis and osteopenia: a pilot study.

OBJECTIVES: Osteoporosis is characterized by slow deterioration in bone mass and disruption of its structure, leading to an increased risk of bone fractures. Gut microbiota plays an important role in the transport and absorption of nutrients needed for bone health. Akkermansia muciniphila is one of the gut microbiota members that its beneficial role in prevention of metabolic disorder was suggested. The aim of the current pilot study was the assessment of fecal A. muciniphila in patients with osteoporosis and osteopenia. METHODS: A total of 36 subjects including eight with osteoporosis (three men and five women), eight with osteopenia (two men and six women), and 20 normal controls (six men and 14 women) were selected. Microbial genome was extracted from fresh stool samples. The bacterial load was determined by quantitative real-time PCR using 16S rRNA specific primers. RESULTS: The participants' mean age in the osteoporosis, osteopenia and control groups were 61.71, 45 and 45.05 years, respectively. The majority of osteoporosis patients were post-menopause women, while in osteopenia group was pre-menopause. There were significant differences in terms of age, T-score, Z-score, and menopause among groups (P value < 0.05). The presence of A. muciniphila was higher in the healthy group compared to osteopenia group; however, these differences were not statistically significant. CONCLUSIONS: In conclusion, however, there was no statistically significant difference between the study groups; it seems that the load of A. muciniphila may be related to bone health. Further in vivo and in vitro studies are needed to investigate the immunological and biochemical pathways.

Targeting TMAO and its metabolic pathway for cardiovascular diseases treatment.

Given the prevalence of cardiovascular diseases (CVDs), as one of the most important non-communicable diseases (NCDs), the recognition of diagnostic biomarkers and potential treatment methods is very crucial. Today gut microbiota composition and its derived metabolites modification are known as one of the recent therapeutic strategies. Studies show that Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that may be involved in the development of cardiovascular diseases, including ischemic disease and atherosclerosis, atrial fibrillation and arrhythmia, and heart failure. Due to existing some disagreements in this manner, future studies are needed to obtain a definitive sight of the association between this metabolite and CVDs. TMAO may be beneficial as a prognostic marker, which represents the degree of gut microbiota dysbiosis and subsequently CVD events and also different therapies methods based on TMAO and its metabolic pathways can be the target of clinical trial on cardiovascular disease and/or its prevention.

Probiotics as a Complementary Therapy for Management of Obesity: A Systematic Review.

BACKGROUND: Considering the observed role of probiotics in modulating gut microbiome, probiotics are discussed to be one potential complementary therapy for obesity management in recent years. The aim of the present study was to systematically review the meta-analyses of controlled trials and investigate the effects of probiotics on obesity. METHODS: A comprehensive search was conducted on PubMed, Web of Science, and Cochrane Library web databases up to May 2020. Inclusion criteria were meta-analyses of controlled trials which evaluated the impact of probiotics on obesity in English language. Meta-analyses done on pregnant women, children, animal studies, or the effect of prebiotics on anthropometric indices were excluded. RESULTS: Within 325 recorded studies, 20 studies met the inclusion criteria consisting of 16676 overweight/obese adults with different underlying disorders such as nonalcoholic fatty liver disease (NAFLD), or polycystic ovary syndrome (PCOS). The length of intervention varied from 2 to 26 weeks. Results of meta-analyses have shown a moderate effect of probiotics on body weight in overweight/obese adults: from -0.526 kg/m2 (95% CI: -0.810, -0.247) to -0.25 kg/m2 (95% CI: -0.33, -0.17). Body mass index (BMI) was changed from -1.46 kg/m2 (95% CI: -2.44, -0.48) to -1.08 kg/m2 (95% CI: -2.05, -0.11) in NAFLD. Probiotics could reduce BMI from -0.36 kg/m2 (95% CI: -0.74, 0.02) to -0.29 kg/m2 (95% CI: -0.54, -0.03) in patients with PCOS. CONCLUSION: It seems that the probiotic products could have beneficial effects as an adjunct therapy for care and management of obesity when used in high dose. However, due to heterogeneity of included studies, it is required to confirm our results by more meta-analyses of clinical trials.

Natural Derived Nasal Spray; A Proposed Approach for COVID-19 Disease Control.

Considering the importance of COVID-19 disease pandemic, emerged by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in line with other studies to find appropriate prevention or treatment methods for this virus infection, our study objective was proposing the use of natural derived ingredients as an approach for COVID-19 disease control. Here we reviewed previous studies on natural derived nasal sprays andfound that some known natural derived ingredients have antiviral properties, so their topical use as a nasalspray is effective in reducing the symptoms of respiratory infections. Moreover, such nasal sprays also have thepotential of decreasing viral load, including titer of coronaviruses, in the nasal cavity. It seems that the use ofcarrageenan or other herbal ingredients in the nasal spray may block the SARS-CoV-2 virus from entering thelung cells of an affected person and can also prevent virus transmission to other susceptible persons. Further,noticing what we know about the novel 2019 coronavirus so far, we suggested carrageenan that has an unspecific physical antiviral activity and some other natural derived ingredients, as a choice in coping with SARS-CoV-2 virus infection.

Global scientific output trend for Akkermansia muciniphila research: a bibliometric and scientometric analysis.

BACKGROUND: Akkermansia muciniphila is an anaerobic bacterium residing in the healthy intestinal tract of host and its quantity has a negative correlation with various host diseases. This study for the first time provides a holistic bibliometric aspect of Akkermansi muciniphila research in the literature and shows the hot topic terms of these articles in any period of time. METHODS: Scopus database was selected to retrieve documents relevant to Akkermansia muciniphila in any language up to 2019. The bibliometric profile of Akkermansia muciniphila articles including subject area, year distribution, citations, institutions, journals, authors, and countries was systematically characterized and the collaboration networks of authors and countries as well as the burst detection algorithm of the words in the titles, abstracts and keywords were visualized. RESULTS: There is a progressive growing trend in research on Akkermansia from 2004 to 2019 with a total of 566 articles during this period. Out of 353 original articles, there are 194 animal studies (155 studies on mice) and 112 human studies. Also, 65 various diseases were investigated in these studies. The most focused conditions are obesity (71 articles) and type2 diabetes (39 articles). The United States is the leading country on Akkermansia publications (n = 132), followed by China (n = 95). Frontiers in Microbiology is the most dominant journal with 23 Akkermansia publications. In addition, "cancer" is the hot topic of recent Akkermansia research. CONCLUSION: Akkermansia research is of progressive interest during the last decade and the studies on this subject move towards its relationship with cancer and its promising effect on health.

Main gut bacterial composition differs between patients with type 1 and type 2 diabetes and non-diabetic adults.

BACKGROUND: Regarding the role of gut microbial dysbiosis in hyperglycemia, we aimed to compare the main gut bacterial composition among type 1 and type 2 diabetic patients and healthy non-diabetic adults. METHODS: A total of 110 adult subjects (49 patients diagnosed with type 2 diabetes, 21 patients diagnosed with type 1 diabetes and 40 healthy persons) were included in this case-control study. The intestinal microbiota composition was investigated by quantitative real-time polymerase chain reaction (qPCR) method targeting bacterial 16S rRNA gene. Comparison between three groups was done using one-way analysis of variance. RESULTS: The participants' mean age in the type 1 diabetes, type 2 diabetes and control groups was 35.4, 57.2 and 38.0 years, respectively. Higher level of Escherichia, Prevotella and Lactobacillus was observed in both type 1 and type 2 diabetic patients compared with the healthy group (P ˂0.001). In contrast, bacterial load of Bifidobacterium, Roseburia and Bacteroides was higher in healthy control group (P < 0.05). Faecalibacterium was significantly lower in type 1 diabetic patients compared with the other two groups (P ˂0.001). No significant difference was found in Akkermansia level among three groups. CONCLUSIONS: Gut microbial alterations have been observed among patients suffering from type 1 and type 2 diabetes mellitus and healthy control adults. Butyrate producing genera including Roseburia and Faecalibacterium decreased while Escherichia, Prevotella and Lactobacillus increased in diabetic patients compared to healthy subjects. Modulating approaches of gut microbiota composition could be helpful in diabetes management.

Effect of probiotic foods and supplements on blood pressure: a systematic review of meta-analyses studies of controlled trials.

OBJECTIVE: Recent evidences suggested that hypertension was associated with changes in gut microbiota composition. As intervention with probiotics might be considered as one of the approaches for modulating gut microbiota, the objective of the present study was to systematically review the meta-analyses of controlled trials (CTs) to elucidate the effects of probiotics on blood pressure. METHODS: We searched PubMed, Web of Science, and Cochrane Library databases until November 2019 to explore all the meta-analyses conducted on the CTs assessing the efficacy of probiotics in the management of blood pressure (BP). Meta-analyses performed on in vitro, animal or observational studies were excluded from the study. References of the included studies were also screened to obtain further eligible publications. RESULTS: From the 111 records which were identified during the literature search, 5 meta-analyses met the selection criteria. Total sample size was 2703 subjects (1009 subjects with type 2 diabetes mellitus (T2DM)), aged 12-75 years from both sexes. Results of meta-analyses have been shown a moderate effect of probiotics on BP in hypertensive adults with/without T2DM; from 3.10 to 5.04 mmHg for systolic blood pressure (SBP) and from 0.39 to 3.84 mmHg for diastolic blood pressure (DBP) after 3-24 weeks consumption. These effects were greater in adults with BP ≥ 130/85, by dairy products, by Asian fermented products with multiple species and higher dose of probiotics (≥ 1011 colony forming units (CFU)). CONCLUSION: It seems probiotic foods and supplements which were contained high dose multiple species of probiotic bacteria could be more effective in BP control.

The importance of interaction between MicroRNAs and gut microbiota in several pathways.

The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. Microbiota disruption affects the immune function, metabolism, and causes several diseases. Therefore, understanding how the microbiome is adjusted, and identifying methods for manipulating it is critical. Studies have found that there is an inverse association between MicroRNAs (miRNAs) abundance and microbe abundance. miRNAs are known to be engaged in post-transcription regulation of cell-autonomous gene expression. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. Here, we review recent studies on the role of miRNAs as a component of outer membrane vesicles (OMVs) in the composition of gut microbiota and their significance in the human situation of health and diseases and discuss their effect on inflammatory responses and dysbiosis. Further, we explain how probiotics exert influence on the expression of miRNAs.

Targeting obesity management through gut microbiota modulation by herbal products: A systematic review.

OBJECTIVES: The gut dysbiosis has been implicated as a mediator to obesity and its manipulation could be an appropriate approach to sustainable weight loss. In this systematic review, our primary objective was to assess the potential manipulation of gut microbiota by herbal products in obesity. MATERIALS AND METHODS: We did a comprehensive search in PubMed, Web of Science, Scopus and Cochrane databases for all clinical trials and animal studies exploring the effects of various herbal products on gut microbiota composition in obesity documented up to May 2017. RESULTS: Our initial search yielded 2766 articles. After screening abstracts and full texts, 68 articles were included (55 animal studies and 13 clinical trials). The studies differed in their methodologies, type of interventions and intervention lengths. The weight loss was only reported in 23% of trials and in 64% of animal studies. An increasing tendency in Bifidobacterium species and butyrate-producing bacteria such as Faecalibacterium prausnitzii were observed after consuming non-digestible carbohydrates, although these changes did not always correlate with weight loss. Supplementation with high concentration of polyphenols reduced body weight gain in animal studies and inhibited growth of detrimental species such as Clostridia and Enterobacteria while the growth of Lactic acid bacteria and Akkermansia muciniphila is enriched. CONCLUSIONS: Alteration of gut microbiota after interventions has been affected by the baseline composition of gut microbiota. This systematic review shows that consumption of herbal products might have beneficial effects on restoring healthy gut microbiome besides body fat reduction.

Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial.

OBJECTIVE: The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD). DESIGN: Randomized double-blind parallel-group clinical trial. METHODS: Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. RESULTS: Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigella abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002). CONCLUSIONS: Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.