Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health

This article reviews the current evidence associating gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of composition, their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivatives, vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased production of hydrogen sulfide and the resultant decreased production of butyrate, in turn affect substrate oxidation and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome associated with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis.

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Novel Oral Anticoagulants in Peripheral Artery Disease: Current Evidence

Current Pharmaceutical Design ◽

10.2174/1381612825666181226151959 ◽

2019 ◽

Vol 24 (38) ◽

pp. 4511-4515 ◽

Cited By ~ 1

Author(s):

A. Koutsoumpelis ◽

C. Argyriou ◽

K.M. Tasopoulou ◽

E.I. Georgakarakos ◽

G.S. Georgiadis

Keyword(s):

Peripheral Artery Disease ◽

Oral Anticoagulants ◽

Novel Oral Anticoagulants ◽

Current Evidence ◽

Peripheral Artery ◽

Cardiac Events ◽

Traditional Therapy ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

Artery Disease

Background: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. Methods: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. Results: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. Conclusion: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.

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Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment

Current Vascular Pharmacology ◽

10.2174/1570161117666190619143842 ◽

2020 ◽

Vol 18 (5) ◽

pp. 431-446 ◽

Cited By ~ 3

Author(s):

George E. Fragoulis ◽

Ismini Panayotidis ◽

Elena Nikiphorou

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Current Evidence ◽

Pharmacological Intervention ◽

Cvd Risk ◽

The Past ◽

Increased Risk ◽

Cv Disease ◽

Obesity Hypertension ◽

Inflammatory Burden

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.

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Association of Urinary and Plasma Levels of Trimethylamine N-Oxide (TMAO) with Foods

Nutrients ◽

10.3390/nu13051426 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1426

Author(s):

Mauro Lombardo ◽

Giovanni Aulisa ◽

Daniele Marcon ◽

Gianluca Rizzo ◽

Maria Grazia Tarsisano ◽

...

Keyword(s):

Gut Microbiota ◽

Fish Consumption ◽

Plasma Levels ◽

Cooking Methods ◽

Saltwater Fish ◽

Increased Risk ◽

Mediator Role ◽

Fish And Shellfish ◽

The Relationship

Introduction: Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. Methods: 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords “TMAO” AND “egg” OR “meat” OR “fish” OR “dairy” OR “vegetables” OR “fruit” OR “food” in December 2020. Results: A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Discussion: Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.

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Defining a research agenda for youth sport specialisation in the USA: the AMSSM Youth Early Sport Specialization Summit

British Journal of Sports Medicine ◽

10.1136/bjsports-2020-102699 ◽

2021 ◽

Vol 55 (3) ◽

pp. 135-143

Author(s):

Stephanie A Kliethermes ◽

Stephen W Marshall ◽

Cynthia R LaBella ◽

Andrew M Watson ◽

Joel S Brenner ◽

...

Keyword(s):

Research Agenda ◽

Sport Participation ◽

Youth Sport ◽

Well Being ◽

Medical Society ◽

Current Evidence ◽

Future Research ◽

Long Term Effects ◽

Increased Risk ◽

The Usa

Sport specialisation is becoming increasingly common among youth and adolescent athletes in the USA and many have raised concern about this trend. Although research on sport specialisation has grown significantly, numerous pressing questions remain pertaining to short-term and long-term effects of specialisation on the health and well-being of youth, including the increased risk of overuse injury and burnout. Many current elite athletes did not specialise at an early age. Methodological and study design limitations impact the quality of current literature, and researchers need to prioritise pressing research questions to promote safe and healthy youth sport participation. The American Medical Society for Sports Medicine hosted a Youth Early Sport Specialization Summit in April 2019 with the goal of synthesising and reviewing current scientific knowledge and developing a research agenda to guide future research in the field based on the identified gaps in knowledge. This statement provides a broad summary of the existing literature, gaps and limitations in current evidence and identifies key research priorities to help guide researchers conducting research on youth sport specialisation. Our goals are to help improve the quality and relevance of research on youth sport specialisation and to ultimately assure that opportunities for healthy and safe sport participation continue for all youth.

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The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, l-carnitine and related precursors by the human gut microbiota

European Journal of Nutrition ◽

10.1007/s00394-021-02572-6 ◽

2021 ◽

Author(s):

Priscilla Day-Walsh ◽

Emad Shehata ◽

Shikha Saha ◽

George M. Savva ◽

Barbora Nemeckova ◽

...

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Human Colon ◽

Human Studies ◽

Bacterial Strains ◽

Increased Risk ◽

Carnitine Metabolism ◽

Registration Number ◽

Vitro Model

Abstract Purpose Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.

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Surgical treatment of recalcitrant gastroesophageal reflux disease in patients with systemic sclerosis: a systematic review

Langenbeck s Archives of Surgery ◽

10.1007/s00423-021-02118-8 ◽

2021 ◽

Author(s):

Alberto Aiolfi ◽

Mario Nosotti ◽

Kazuhide Matsushima ◽

Carolina Perali ◽

Cristina Ogliari ◽

...

Keyword(s):

Systematic Review ◽

Systemic Sclerosis ◽

Surgical Treatment ◽

Gastroesophageal Reflux Disease ◽

Gastroesophageal Reflux ◽

Reflux Disease ◽

Current Data ◽

Current Evidence ◽

Increased Risk

Abstract Introduction Gastroesophageal reflux disease (GERD) is frequently seen in patients with systemic sclerosis (SSc). Long-standing GERD may cause esophagitis, long-segment strictures, and Barrett’s esophagus and may worsen pre-existing pulmonary fibrosis with an increased risk of end-stage lung disease. Surgical treatment of recalcitrant GERD remains controversial. The purpose of this systematic review was to summarize the current data on surgical treatment of recalcitrant GERD in SSc patients. Materials and methods A systematic literature review according to PRISMA and MOOSE guidelines. PubMed, EMBASE, and Web of Science databases were consulted. Results A total of 101 patients were included from 7 studies. The age ranged from 34 to 61 years and the majority were females (73.5%). Commonly reported symptoms were heartburn (92%), regurgitation (77%), and dysphagia (74%). Concurrent pulmonary disease was diagnosed in 58% of patients. Overall, 63 patients (62.4%) underwent open fundoplication, 17 (16.8%) laparoscopic fundoplication, 15 (14.9%) Roux en-Y gastric bypass (RYGB), and 6 (5.9%) esophagectomy. The postoperative follow-up ranged from 12 to 65 months. Recurrent symptoms were described in up to 70% and 30% of patients undergoing fundoplication and RYGB, respectively. Various symptoms were reported postoperatively depending on the type of surgical procedures, anatomy of the valve, need for esophageal lengthening, and follow-up. Conclusions The treatment of recalcitrant GERD in SSc patients is challenging. Esophagectomy should be reserved to selected patients. Minimally invasive RYGB appears feasible and safe with promising preliminary short-term results. Current evidence is scarce while a definitive indication about the most appropriate surgical treatment is lacking.

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Gut Microbiota Prevents Sugar Alcohol-Induced Diarrhea

Nutrients ◽

10.3390/nu13062029 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2029

Author(s):

Kouya Hattori ◽

Masahiro Akiyama ◽

Natsumi Seki ◽

Kyosuke Yakabe ◽

Koji Hase ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Bacteria ◽

Food Science ◽

Sugar Alcohol ◽

Processed Food ◽

Phosphotransferase System ◽

Sugar Alcohols ◽

E Coli ◽

The Family ◽

Rdna Analysis

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.

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The Effectiveness of Acupuncture in Management of Functional Constipation: A Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6137450 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Lu Wang ◽

Mingmin Xu ◽

Qianhua Zheng ◽

Wei Zhang ◽

Ying Li

Keyword(s):

Quality Of Life ◽

Meta Analysis ◽

Safety Evaluation ◽

Functional Constipation ◽

Responder Rate ◽

Current Evidence ◽

Cochrane Library ◽

China National Knowledge Infrastructure ◽

Increased Risk

Objective. The purpose of this study was to assess the effectiveness and safety of acupuncture for functional constipation (FC). Methods. A rigorous literature search was performed in English (PubMed, Web of Science, the Cochrane Library, and EMBASE) and Chinese (China National Knowledge Infrastructure (CNKI), Chinese Biological Medical (CBM), Wanfang database, and China Science and Technology Journal (VIP)) electronic databases from their inception to October 2019. Included randomized controlled trials (RCTs) compared acupuncture therapy with sham acupuncture or pharmacological therapies. The outcome measures were evaluated, including the primary outcome of complete spontaneous bowel movement (CSBM) and secondary outcomes of Bristol Stool Form Scale (BSFS), constipation symptoms scores (CSS), responder rate, the Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaire, and safety evaluation. Meta-analysis was performed by using RevMan5.3. Results. The merged data of 28 RCTs with 3525 participants indicated that acupuncture may be efficient for FC by increasing CSBMs (p<0.00001; MD = 0.84 [95% CI, 0.65 to 1.03]; I2 = 0%) and improving constipation symptoms (p=0.03; SMD = −0.4 [95% CI, −0.78 to −0.03]; I2 = 74%), stool formation (p<0.00001; MD = 0.24 [95% CI, 0.15 to 0.34]; I2 = 0%), quality of life (p<0.00001; N = 1, MD = −0.33 [95% CI, −0.45 to −0.21]), and responder rates (p=0.02; RR = 2.16; [95% CI, 1.1 to 4.24]; I2 = 69%) compared with the effects of sham treatment. No increased risk of adverse events was observed (p=0.44; RR = 1.18; [95% CI, 0.77 to 1.81]; I2 = 0%). With regard to medication comparisons, the pooled data indicated that acupuncture was more effective in increasing CSBMs (p=0.004; MD = 0.53 [95% CI, 0.17 to 0.88]; I2 = 88%) and improving patients’ quality of life (p<0.00001; SMD = −0.73 [95% CI, −1.02 to −0.44]; I2 = 64%), with high heterogeneity. However, there were no significant differences in responder rate (p=0.12; RR = 1.31; [95% CI, 0.94 to 1.82]; I2 = 53%), BSFS (p=0.5; MD = 0.17 [95% CI, −0.33 to 0.68]; I2 = 93%), or CSS (p=0.05; SMD = −0.62 [95% CI, −1.23 to −0.01]; I2 = 89%). Regarding safety evaluation, acupuncture was safer than medications (p<0.0001; RR = 0.3; [95% CI, 0.18 to 0.52]; I2 = 30%). Conclusions. Current evidence suggests that acupuncture is an efficient and safe treatment for FC. Acupuncture increased stool frequency, improved stool formation, alleviated constipation symptoms, and improved quality of life. However, the evidence quality was relatively low and the relationship between acupuncture and drugs is not clear. More high-quality trials are recommended in the future. PROSPERO registration number: CRD42019143347.

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The Relationship between Frequently Used Glucose-Lowering Agents and Gut Microbiota in Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2018/1890978 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 7

Author(s):

You Lv ◽

Xue Zhao ◽

Weiying Guo ◽

Ying Gao ◽

Shuo Yang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Short Chain Fatty Acids ◽

Current Evidence ◽

Diabetic Patients ◽

Glucose Lowering ◽

Patients With Diabetes ◽

Gastrointestinal Side Effects ◽

Underlying Mechanisms

Metabolic diseases, especially diabetes mellitus, have become global health issues. The etiology of diabetes mellitus can be attributed to genetic and/or environmental factors. Current evidence suggests the association of gut microbiota with metabolic diseases. However, the effects of glucose-lowering agents on gut microbiota are poorly understood. Several studies revealed that these agents affect the composition and diversity of gut microbiota and consequently improve glucose metabolism and energy balance. Possible underlying mechanisms include affecting gene expression, lowering levels of inflammatory cytokines, and regulating the production of short-chain fatty acids. In addition, gut microbiota may alleviate adverse effects caused by glucose-lowering agents, and this can be especially beneficial in diabetic patients who experience severe gastrointestinal side effects and have to discontinue these agents. In conclusion, gut microbiota may provide a novel viewpoint for the treatment of patients with diabetes mellitus.

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