Significance of Gut Microbiota and Short-Chain Fatty Acids in Heart Failure

Heart failure (HF), as the terminal stage of various heart diseases, seriously threatens an individual’s life, health, and quality of life. Emerging evidence has shown that the gut microbiota comprises an important component of human physiology and metabolic homeostasis, and can directly or indirectly affect the metabolic health of the host through metabolites. Upon in-depth study of intestinal microecology, the “gut-heart axis” appears to provide a novel direction for HF research. Thus, this review primarily focuses on the relationship between the gut microbiota and its major metabolites—i.e., short-chain fatty acids (SCFAs)—and HF. It explores the mechanisms underlying HF and its effective treatment by targeting SCFAs to optimize current HF treatment and thus improve the quality of patients’ lives.     

Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.     

Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg⁻¹) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.     

Gut Microbiota Profile and Its Association with Clinical Variables and Dietary Intake in Overweight/Obese and Lean Subjects: A Cross-Sectional Study

We aimed to differentiate gut microbiota composition of overweight/obese and lean subjects and to determine its association with clinical variables and dietary intake. A cross-sectional study was performed with 96 overweight/obese subjects and 32 lean subjects. Anthropometric parameters were positively associated with Collinsella aerofaciens, Dorea formicigenerans and Dorea longicatena, which had higher abundance the overweight/obese subjects. Moreover, different genera of Lachnospiraceae were negatively associated with body fat, LDL and total cholesterol. Saturated fatty acids (SFAs) were negatively associated with the genus Intestinimonas, a biomarker of the overweight/obese group, whereas SFAs were positively associated with Roseburia, a biomarker for the lean group. In conclusion, Dorea formicigenerans, Dorea longicatena and Collinsella aerofaciens could be considered obesity biomarkers, Lachnospiraceae is associated with lipid cardiovascular risk factors. SFAs exhibited opposite association profiles with butyrate-producing bacteria depending on the BMI. Thus, the relationship between diet and microbiota opens new tools for the management of obesity.     

Analysis of the Ability of Capsaicin to Modulate the Human Gut Microbiota In Vitro

Previous studies on capsaicin, the bioactive compound in chili peppers, have shown that it may have a beneficial effect in vivo when part of a regular diet. These positive health benefits, including an anti-inflammatory potential and protective effects against obesity, are often attributed to the gut microbial community response to capsaicin. However, there is no consensus on the mechanism behind the protective effect of capsaicin. In this study, we used an in vitro model of the human gut microbiota to determine how regular consumption of capsaicin impacts the gut microbiota. Using a combination of NextGen sequencing and metabolomics, we found that regular capsaicin treatment changed the structure of the gut microbial community by increasing diversity and certain SCFA abundances, particularly butanoic acid. Through this study, we determined that the addition of capsaicin to the in vitro cultures of the human gut microbiome resulted in increased diversity of the microbial community and an increase in butanoic acid. These changes may be responsible for the health benefits associated with CAP consumption.     

Association of the Maternal Gut Microbiota/Metabolome with Cord Blood CCL17

Chemokine (C-C motif) ligand 17 (CCL17) is a pro-allergic factor: high CCL17 levels in cord blood (CB) precede later allergic predisposition. Short-chain fatty acid (SCFA) treatment during pregnancy has been shown to protect mouse pups against allergic diseases. The maternal microbial metabolome during pregnancy may affect fetal allergic immune responses. We therefore examined the associations between CB CCL17 and gut SCFA levels in healthy pregnant Japanese women. CB CCL17 serum levels at birth, and maternal non-specific IgE levels in maternal sera at 32 weeks of gestation were measured. Maternal stool samples were collected at 12 (n = 59) and 32 (n = 58) weeks of gestation for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. The CB CCL17 levels correlated negatively with butyrate concentrations and positively with isobutyrate at 12 weeks; CB CCL17 correlated positively with valerate and lactate at 32 weeks. Similarly, butyrate levels correlated negatively with maternal non-specific IgE levels, whereas the lactate concentration correlated positively with IgE levels. At 32 weeks, the Shannon diversity index (SDI) of Firmicutes and Proteobacteria correlated negatively with CB CCL17 levels, while those of the total microbiota correlated positively with the CB CCL17 levels. These metabolites may alter fetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring.     

Prebiotics and the Human Gut Microbiota: From Breakdown Mechanisms to the Impact on Metabolic Health

The colon harbours a dynamic and complex community of microorganisms, collectively known as the gut microbiota, which constitutes the densest microbial ecosystem in the human body. These commensal gut microbes play a key role in human health and diseases, revealing the strong potential of fine-tuning the gut microbiota to confer health benefits. In this context, dietary strategies targeting gut microbes to modulate the composition and metabolic function of microbial communities are of increasing interest. One such dietary strategy is the use of prebiotics, which are defined as substrates that are selectively utilised by host microorganisms to confer a health benefit. A better understanding of the metabolic pathways involved in the breakdown of prebiotics is essential to improve these nutritional strategies. In this review, we will present the concept of prebiotics, and focus on the main sources and nature of these components, which are mainly non-digestible polysaccharides. We will review the breakdown mechanisms of complex carbohydrates by the intestinal microbiota and present short-chain fatty acids (SCFAs) as key molecules mediating the dialogue between the intestinal microbiota and the host. Finally, we will review human studies exploring the potential of prebiotics in metabolic diseases, revealing the personalised responses to prebiotic ingestion. In conclusion, we hope that this review will be of interest to identify mechanistic factors for the optimization of prebiotic-based strategies.     

Effects of Oats,Tartary Buckwheat,and Foxtail Millet Supplementation on Lipid Metabolism,Oxido-Inflammatory Responses,Gut Microbiota,and Colonic SCFA Composition in High-Fat Diet Fed Rats

Coarse cereals rich in polyphenols, dietary fiber, and other functional components exert multiple health benefits. We investigated the effects of cooked oats, tartary buckwheat, and foxtail millet on lipid profile, oxido-inflammatory responses, gut microbiota, and colonic short-chain fatty acids composition in high-fat diet (HFD) fed rats. Rats were fed with a basal diet, HFD, oats diet (22% oat in HFD), tartary buckwheat diet (22% tartary buckwheat in HFD), and foxtail millet diet (22% foxtail millet in HFD) for 12 weeks. Results demonstrated that oats and tartary buckwheat attenuated oxidative stress and inflammatory responses in serum, and significantly increased the relative abundance of Lactobacillus and Romboutsia in colonic digesta. Spearman’s correlation analysis revealed that the changed bacteria were strongly correlated with oxidative stress and inflammation-related parameters. The concentration of the butyrate level was elevated by 2.16-fold after oats supplementation. In addition, oats and tartary buckwheat significantly downregulated the expression of sterol regulatory element-binding protein 2 and peroxisome proliferator-activated receptors γ in liver tissue. In summary, our results suggested that oats and tartary buckwheat could modulate gut microbiota composition, improve lipid metabolism, and decrease oxidative stress and inflammatory responses in HFD fed rats. The present work could provide scientific evidence for developing coarse cereals-based functional food for preventing hyperlipidemia.     

Specific Strains of Faecalibacterium prausnitzii Ameliorate Nonalcoholic Fatty Liver Disease in Mice in Association with Gut Microbiota Regulation

Evidence linking Faecalibacterium prausnitzii abundance to nonalcoholic fatty liver disease (NAFLD) is accumulating; however, the causal relationship remains obscure. In this study, 12 F. prausnitzii strains were orally administered to high fat diet fed C57BL/6J mice for 12 weeks to evaluate the protective effects of F. prausnitzii on NAFLD. We found that five F. prausnitzii strains, A2-165, LB8, ZF21, PL45, and LC49, significantly restored serum lipid profiles and ameliorated glucose intolerance, adipose tissue dysfunction, hepatic steatosis, inflammation, and oxidative stress in a mouse model of NAFLD. Moreover, two strains, LC49 and LB8, significantly enhanced short-chain fatty acid (SCFA) production and modulated the gut microbiota. Based on the combined analysis of linear discriminant analysis effect size and microbial communities, the core microbiome related to NAFLD comprised Odoribacter, Roseburia, Erysipelatoclostridium, Tyzzerella, Faecalibaculum, Blautia, and Acetatifactor, and the last five genera can be reversed by treatment with the LC49 and LB8 strains. Additionally, the LC49 and LB8 strains enriched Lactobacillus, Ileibacterium, Faecalibacterium, Dubosiella, and Bifidobacterium and downregulated pathways involving carbohydrate metabolism, amino acid metabolism, and fatty acid biosynthesis. Interestingly, LC49 supplementation also upregulated tryptophan metabolism, glutathione metabolism, and valine, leucine, and isoleucine degradation, which might be related to NAFLD prevention. Collectively, F. prausnitzii LC49 and LB8 exerted considerable anti-NAFLD and microbiota-regulating effects, indicating their potential as probiotic agents for NAFLD treatment.     

Microbiota Changes in Fathers Consuming a High Prebiotic Fiber Diet Have Minimal Effects on Male and Female Offspring in Rats

Background: Consuming a diet high in prebiotic fiber has been associated with improved metabolic and gut microbial parameters intergenerationally, although studies have been limited to maternal intake with no studies examining this effect in a paternal model. Method: Male Sprague Dawley rats were allocated to either (1) control or (2) oligofructose-supplemented diet for nine weeks and then mated. Offspring consumed control diet until 16 weeks of age. Bodyweight, body composition, glycemia, hepatic triglycerides, gastrointestinal hormones, and gut microbiota composition were measured in fathers and offspring. Results: Paternal energy intake was reduced, while satiety inducing peptide tyrosine tyrosine (PYY) gut hormone was increased in prebiotic versus control fathers. Increased serum PYY persisted in female prebiotic adult offspring. Hepatic triglycerides were decreased in prebiotic fathers with a similar trend (p = 0.07) seen in female offspring. Gut microbial composition showed significantly reduced alpha diversity in prebiotic fathers at 9 and 12 weeks of age (p < 0.001), as well as concurrent differences in beta diversity (p < 0.001), characterized by differences in Bifidobacteriaceae, Lactobacillaceae and Erysipelotrichaceae, and particularly Bifidobacterium animalis. Female prebiotic offspring had higher alpha diversity at 3 and 9 weeks of age (p < 0.002) and differences in beta diversity at 15 weeks of age (p = 0.04). Increases in Bacteroidetes in female offspring and Christensenellaceae in male offspring were seen at nine weeks of age. Conclusions: Although paternal prebiotic intake before conception improves metabolic and microbiota outcomes in fathers, effects on offspring were limited with increased serum satiety hormone levels and changes to only select gut bacteria.     

Dietary Fibre Intervention for Gut Microbiota,Sleep, and Mental Health in Adults with Irritable Bowel Syndrome: A Scoping Review

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder affecting 4–5% of the global population. This disorder is associated with gut microbiota, diet, sleep, and mental health. This scoping review therefore aims to map existing research that has administrated fibre-related dietary intervention to IBS individuals and reported outcomes on at least two of the three following themes: gut microbiota, sleep, and mental health. Five digital databases were searched to identify and select papers as per the inclusion and exclusion criteria. Five articles were included in the assessment, where none reported on all three themes or the combination of gut microbiota and sleep. Two studies identified alterations in gut microbiota and mental health with fibre supplementation. The other three studies reported on mental health and sleep outcomes using subjective questionnaires. IBS-related research lacks system biology-type studies targeting gut microbiota, sleep, and mental health in patients undergoing diet intervention. Further IBS research is required to explore how human gut microbiota functions (such as short-chain fatty acids) in sleep and mental health, following the implementation of dietary pattern alteration or component supplementation. Additionally, the application of objective sleep assessments is required in order to detect sleep change with more accuracy and less bias.     

Bifidobacterium adolescentis Is Effective in Relieving Type 2 Diabetes and May Be Related to Its Dominant Core Genome and Gut Microbiota Modulation Capacity

The prevalence of diabetes mellitus is increasing globally. Probiotics have been shown to be an effective intervention for diabetes. This study focused on the relieving effects and possible mechanisms of 16 strains of two dominant Bifidobacterium species (B. bifidum and B. adolescentis, which exist in the human gut at different life stages) on type 2 diabetes (T2D). The results indicated that more B. adolescentis strains appeared to be superior in alleviating T2D symptoms than B. bifidum strains. This effect was closely related to the ability of B. adolescentis to restore the homeostasis of the gut microbiota, increase the abundance of short-chain fatty acid-producing flora, and alleviate inflammation in mice with T2D. In addition, compared with B. bifidum, B. adolescentis had a higher number of core genes, and these genes were more evolutionarily stable, including unique environmental tolerance, carbon and nitrogen utilization genes, and a blood sugar regulation gene, glgP. This may be one of the reasons why B. adolescentis is more likely to colonize in the adult gut and show a superior ability to relieve T2D. This study provides insights into future studies aimed at investigating probiotics for the treatment of metabolic diseases.     

Gut Microbiota Profile in Adults Undergoing Bariatric Surgery: A Systematic Review

Gut microbiota (GM) after bariatric surgery (BS) has been considered as a factor associated with metabolic improvements and weight loss. In this systematic review, we evaluate changes in the GM, characterized by 16S rRNA and metagenomics techniques, in obese adults who received BS. The PubMed, Scopus, Web of Science, and LILACS databases were searched. Two independent reviewers analyzed articles published in the last ten years, using Rayyan QCRI. The initial search resulted in 1275 documents, and 18 clinical trials were included after the exclusion criteria were applied. The predominance of intestinal bacteria phyla varied among studies; however, most of them reported a greater amount of Bacteroidetes (B), Proteobacteria (P), and diversity (D) after BS. Firmicutes (F), B, and the (F/B) ratio was inconsistent, increasing or decreasing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were conducted, compared to before surgery. There was a reduction in the relative proportion of F. Moreover, a higher proportion of Actinobacteria (A) was observed after RYGB was conducted. However, the same was not identified when SG procedures were applied. Genera abundance and bacteria predominance varied according to the surgical procedure, with limited data regarding the impact on phyla. The present study was approved by PROSPERO, under registration number CRD42020209509.     

Effects of Smoking on the Gut Microbiota in Individuals with Type 2 Diabetes Mellitus

Smoking affects eating habits; however, few studies on smoking and the gut microbiota have reported the effects of diet in detail. This cross-sectional study aimed to determine the association between smoking and the gut microbiota, considering the impact of smoking on dietary intake. Dietary habits and the composition of the gut microbiota were assessed in 195 men with type 2 diabetes (164 non-current smokers and 31 current smokers) using a brief self-administered diet history questionnaire and 16S ribosomal RNA gene sequencing of fecal samples. The data were compared according to the current smoking status of the participants. Current smokers had high alcohol and sugar/sweetener intake and low fruit intake. The proportion of the Coprococcus genus was higher among current smokers. Multiple regression analysis adjusted for current smoking, age, exercise habits, alcohol intake, sugar and sweetener intake, and fruit intake showed that smoking was associated with the proportion of the Coprococcus genus. Current smoking was associated with both dietary intake and composition of the gut microbiota. Although dietary intake should be considered when investigating the association between smoking and the gut microbiota, the results suggest that the direct effect of smoking is more significant.     

The Effects of Time-Restricted Eating on Metabolism and Gut Microbiota: A Real-Life Study

The metabolic benefits of time-restricted eating (TRE) in humans are statistically significant but not clinically relevant. Few data are available about the effects of TRE on the gut microbiota. We compared the effects of a TRE regimen (<12 h feeding; n = 25) with a time-unrestricted (TUE) regimen (>12 h feeding; n = 24), on the clinical and dietary variables and gut-microbiota composition in patients with obesity, who were subjected for 12 weeks to the same caloric restriction. Median weight loss was 4.0 kg and 2.2 kg in the TRE and TUE groups, respectively, with a between-group borderline difference (p = 0.049). No significant between-group difference was found in other dietary, anthropometric, or laboratory variables. There were no substantial between-group differences in alpha and beta diversity or gut-microbiota composition. The TRE group showed a significant increase in the frequency of Lachnospiraceae, Parasutterella, and Romboutsia at the study’s end. A TRE regimen induced small changes both in metabolic/dietary variables and in the gut-microbiota composition, with respect to the TUE. The microbial changes we have found were of uncertain clinical significance.     

The Effects of Ionizing Radiation on Gut Microbiota,a Systematic Review

Background: The human gut microbiota is defined as the microorganisms that collectively inhabit the intestinal tract. Its composition is relatively stable; however, an imbalance can be precipitated by various factors and is known to be associated with various diseases. Humans are daily exposed to ionizing radiation from ambient and medical procedures, and gastrointestinal side effects are not rare. Methods: A systematic search of PubMed, EMBASE, and Cochrane Library databases was conducted. Primary outcomes were changes in composition, richness, and diversity of the gut microbiota after ionizing radiation exposure. Standard methodological procedures expected by Cochrane were used. Results: A total of 2929 nonduplicated records were identified, and based on the inclusion criteria, 11 studies were considered. Studies were heterogeneous, with differences in population and outcomes. Overall, we found evidence for an association between ionizing radiation exposure and dysbiosis: reduction in microbiota diversity and richness, increase in pathogenic bacteria abundance (Proteobacteria and Fusobacteria), and decrease in beneficial bacteria (Faecalibacterium and Bifidobacterium). Conclusions: This review highlights the importance of considering the influence of ionizing radiation exposure on gut microbiota, especially when considering the side effects of abdominal and pelvic radiotherapy. Better knowledge of these effects, with larger population studies, is needed.     

Modulation of the Gut Microbiota Structure with Probiotics and Isoflavone Alleviates Metabolic Disorder in Ovariectomized Mice

The decrease in ovarian hormone secretion that occurs during menopause results in an increase in body weight and adipose tissue mass. Probiotics and soy isoflavones (SIFs) could affect the gut microbiota and exert anti-obesity effects. The objective of this study was to investigate the effects of probiotics and a diet containing SIF (SIF diet) on ovariectomized mice with menopausal obesity, including the gut microbiome. The results demonstrate that Bifidobacterium longum 15M1 can reverse menopausal obesity, whilst the combination of Lactobacillus plantarum 30M5 and a SIF diet was more effective in alleviating menopausal lipid metabolism disorder than either components alone. Probiotics and SIFs play different anti-obesity roles in menopausal mice. Furthermore, 30M5 alters the metabolites of the gut microbiota that increase the circulating estrogen level, upregulates the expression of estrogen receptor α in abdominal adipose tissue and improves the production of short-chain fatty acids (SCFAs). A SIF diet can significantly alter the structure of the fecal bacterial community and enrich the pathways related to SCFAs production. Moreover, 30M5 and a SIF diet acted synergistically to effectively resolve abnormal serum lipid levels in ovariectomized mice, and these effects appear to be associated with regulation of the diversity and structure of the intestinal microbiota to enhance SCFAs production and promote estrogen circulation.     

A Citrus Fruit Extract High in Polyphenols Beneficially Modulates the Gut Microbiota of Healthy Human Volunteers in a Validated In Vitro Model of the Colon

The effect of a Citrus Fruit Extract high in the polyphenols hesperidin and naringin (CFE) on modulation of the composition and activity of the gut microbiota was tested in a validated, dynamic in vitro model of the colon (TIM-2). CFE was provided at two doses (250 and 350 mg/day) for 3 days. CFE led to a dose-dependent increase in Roseburia, Eubacterium ramulus, and Bacteroides eggerthii. There was a shift in production of short-chain fatty acids, where acetate production increased on CFE, while butyrate decreased. In overweight and obesity, acetate has been shown to increase fat oxidation when produced in the distal gut, and stimulate secretion of appetite-suppressive neuropeptides. Thus, the data in the in vitro model point towards mechanisms underlying the effects of the polyphenols in CFE with respect to modulation of the gut microbiota, both in composition and activity. These results should be confirmed in a clinical trial.