-
Nutrients Sep 2023Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the... (Review)
Review
Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all -random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.
Topics: Child; Humans; Cholesterol, LDL; Cross-Sectional Studies; Diet, Ketogenic; Drug Resistant Epilepsy; Multimorbidity; Reproducibility of Results; Seizures; Testosterone; Treatment Outcome; Meta-Analysis as Topic
PubMed: 37836444
DOI: 10.3390/nu15194161 -
Gut Microbes Dec 2023Hepatocellular carcinoma (HCC) has been linked to the gut microbiota, with recent studies revealing the potential of gut-generated responses to influence several arms of... (Review)
Review
Hepatocellular carcinoma (HCC) has been linked to the gut microbiota, with recent studies revealing the potential of gut-generated responses to influence several arms of the immune responses relevant to HCC formation. The pro- or anti-tumor effects of specific bacterial strains or gut microbiota-related metabolites, such as bile acids and short-chain fatty acids, have been highlighted in many human and animal studies. The critical role of the gut microbiota in HCC development has spurred interest in modulating the gut microbiota through dietary interventions, probiotics, and fecal microbiota transplantation as a potential strategy to improve liver cancer outcomes. Encouragingly, preclinical and clinical studies have demonstrated that modulation of the gut microbiota can ameliorate liver function, reduce inflammation, and inhibit liver tumor growth, underscoring the potential of this approach to improve HCC outcomes. As research continues to unravel the complex and dynamic mechanisms underlying the gut-liver axis, the development of safe and effective interventions to target this pathway for liver cancer prevention and treatment appears to be on the horizon, heralding a significant advance in our ongoing efforts to combat this devastating disease.
Topics: Animals; Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Gastrointestinal Microbiome; Bile Acids and Salts
PubMed: 37615334
DOI: 10.1080/19490976.2023.2240031 -
Cell Reports Aug 2023Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and...
Colorectal cancer (CRC) is driven by genomic alterations in concert with dietary influences, with the gut microbiome implicated as an effector in disease development and progression. While meta-analyses have provided mechanistic insight into patients with CRC, study heterogeneity has limited causal associations. Using multi-omics studies on genetically controlled cohorts of mice, we identify diet as the major driver of microbial and metabolomic differences, with reductions in α diversity and widespread changes in cecal metabolites seen in high-fat diet (HFD)-fed mice. In addition, non-classic amino acid conjugation of the bile acid cholic acid (AA-CA) increased with HFD. We show that AA-CAs impact intestinal stem cell growth and demonstrate that Ileibacterium valens and Ruminococcus gnavus are able to synthesize these AA-CAs. This multi-omics dataset implicates diet-induced shifts in the microbiome and the metabolome in disease progression and has potential utility in future diagnostic and therapeutic developments.
Topics: Animals; Mice; Bile Acids and Salts; Microbiota; Gastrointestinal Microbiome; Metabolome; Colorectal Neoplasms
PubMed: 37611587
DOI: 10.1016/j.celrep.2023.112997 -
JAMA Network Open Jul 2023Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Plant-based diets are known to improve cardiometabolic risk in the general population, but their effects on people at high risk of cardiovascular diseases (CVDs) remain inconclusive.
OBJECTIVE
To assess the association of vegetarian diets with major cardiometabolic risk factors, including low-density lipoprotein cholesterol (LDL-C), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and body weight in people with or at high risk of CVDs.
DATA SOURCES
This meta-analysis was registered before the study was conducted. Systematic searches performed included Embase, MEDLINE, CINAHL, and CENTRAL from inception until July 31, 2021.
STUDY SELECTION
Eligible randomized clinical trials (RCTs) that delivered vegetarian diets in adults with or at high risk of CVDs and measured LDL-C, HbA1c or SBP were included. Of the 7871 records screened, 29 (0.4%; 20 studies) met inclusion criteria.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data including demographics, study design, sample size, and diet description, and performed risk of bias assessment. A random-effects model was used to assess mean changes in LDL-C, HbA1c, SBP, and body weight. The overall certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.
MAIN OUTCOMES AND MEASURES
Mean differences between groups in changes (preintervention vs postintervention) of LDL-C, HbA1c, and SBP; secondary outcomes were changes in body weight and energy intake.
RESULTS
Twenty RCTs involving 1878 participants (range of mean age, 28-64 years) were included, and mean duration of intervention was 25.4 weeks (range, 2 to 24 months). Four studies targeted people with CVDs, 7 focused on diabetes, and 9 included people with at least 2 CVD risk factors. Overall, relative to all comparison diets, meta-analyses showed that consuming vegetarian diets for an average of 6 months was associated with decreased LDL-C, HbA1c, and body weight by 6.6 mg/dL (95% CI, -10.1 to -3.1), 0.24% (95% CI, -0.40 to -0.07), and 3.4 kg (95% CI, -4.9 to -2.0), respectively, but the association with SBP was not significant (-0.1 mm Hg; 95% CI, -2.8 to 2.6). The GRADE assessment showed a moderate level of evidence for LDL-C and HbA1c reduction.
CONCLUSIONS AND RELEVANCE
In this study, consuming a vegetarian diet was associated with significant improvements in LDL-C, HbA1c and body weight beyond standard therapy in individuals at high risk of CVDs. Additional high-quality trials are warranted to further elucidate the effects of healthy plant-based diets in people with CVDs.
Topics: Adult; Humans; Middle Aged; Cardiovascular Diseases; Cholesterol, LDL; Glycated Hemoglobin; Vegetarians; Research Design; Body Weight
PubMed: 37490288
DOI: 10.1001/jamanetworkopen.2023.25658 -
Cell Mar 2024The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge...
The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.
Topics: Animals; Humans; Bile Acids and Salts; Metabolomics; Polyamines; Tandem Mass Spectrometry; Gastrointestinal Microbiome; Databases, Chemical
PubMed: 38471500
DOI: 10.1016/j.cell.2024.02.019 -
Hepatology (Baltimore, Md.) Jul 2023NAFLD is characterized by steatosis, hepatic inflammation, and fibrosis, which can develop into NASH. Patients with NAFLD/NASH have increased ductular reaction (DR) and...
BACKGROUND AND AIMS
NAFLD is characterized by steatosis, hepatic inflammation, and fibrosis, which can develop into NASH. Patients with NAFLD/NASH have increased ductular reaction (DR) and biliary senescence. High fat/high cholesterol diet feeding increases biliary senescence, DR, and biliary insulin-like growth factor-1 (IGF-1) expression in mice. p16/IGF-1 converges with fork-head box transcription factor O1 (FOXO1) through E2F1. We evaluated p16 inhibition on NAFLD phenotypes and biliary E2F1/FOXO1/IGF-1 signaling.
APPROACH AND RESULTS
4-week wild-type (C57BL/6J) male mice were fed a control diet (CD) or high fat/high cholesterol diet and received either p16 or control Vivo Morpholino (VM) by tail vein injection 2× during the 16th week of feeding. We confirmed p16 knockdown and examined: (i) NAFLD phenotypes; (ii) DR and biliary senescence; (iii) serum metabolites; and (iv) biliary E2F1/FOXO1/IGF-1 signaling. Human normal, NAFLD, and NASH liver samples and isolated cholangiocytes treated with control or p16 VM were evaluated for p16/E2F1/FOXO1/IGF-1 signaling. p16 VM treatment reduced cholangiocyte and hepatocyte p16. In wild-type high fat/high cholesterol diet mice with control VM, there were increased (i) NAFLD phenotypes; (ii) DR and biliary senescence; (iii) serum metabolites; and (iv) biliary E2F1/FOXO1/IGF-1 signaling; however, p16 VM treatment reduced these parameters. Biliary E2F1/FOX-O1/IGF-1 signaling increased in human NAFLD/NASH but was blocked by p16 VM. In vitro , p16 VM reduced biliary E2f1 and Foxo1 transcription by inhibiting RNA pol II binding and E2F1 binding at the Foxo1 locus, respectively. Inhibition of E2F1 reduced biliary FOXO1 in vitro.
CONCLUSION
Attenuating hepatic p16 expression may be a therapeutic approach for improving NAFLD/NASH phenotypes.
Topics: Animals; Humans; Male; Mice; Cholesterol; Diet, High-Fat; Disease Models, Animal; E2F1 Transcription Factor; Forkhead Box Protein O1; Insulin-Like Growth Factor I; Liver; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Phenotype; Cyclin-Dependent Kinase Inhibitor p16
PubMed: 36799449
DOI: 10.1097/HEP.0000000000000307 -
Nature Metabolism Jun 2024Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular...
Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.
Topics: Animals; Receptors, G-Protein-Coupled; Diabetic Cardiomyopathies; Mice; Male; Female; Fatty Acids; Humans; Mice, Knockout; Bile Acids and Salts; Diet, High-Fat; CD36 Antigens; Myocardium; Lipid Metabolism; Myocytes, Cardiac; Diabetes Mellitus, Experimental
PubMed: 38698281
DOI: 10.1038/s42255-024-01036-5 -
Metabolomics : Official Journal of the... Aug 2023Bees provide essential pollination services for many food crops and are critical in supporting wild plant diversity. However, the dietary landscape of pollen food... (Review)
Review
BACKGROUND
Bees provide essential pollination services for many food crops and are critical in supporting wild plant diversity. However, the dietary landscape of pollen food sources for social and solitary bees has changed because of agricultural intensification and habitat loss. For this reason, understanding the basic nutrient metabolism and meeting the nutritional needs of bees is becoming an urgent requirement for agriculture and conservation. We know that pollen is the principal source of dietary fat and sterols for pollinators, but a precise understanding of what the essential nutrients are and how much is needed is not yet clear. Sterols are key for producing the hormones that control development and may be present in cell membranes, where fatty-acid-containing species are important structural and signalling molecules (phospholipids) or to supply, store and distribute energy (glycerides).
AIM OF THE REVIEW
In this critical review, we examine the current general understanding of sterol and lipid metabolism of social and solitary bees from a variety of literature sources and discuss implications for bee health.
KEY SCIENTIFIC CONCEPTS OF REVIEW
We found that while eusocial bees are resilient to some dietary variation in sterol supply the scope for this is limited. The evidence of both de novo lipogenesis and a dietary need for particular fatty acids (FAs) shows that FA metabolism in insects is analogous to mammals but with distinct features. Bees rely on their dietary intake for essential sterols and lipids in a way that is dependent upon pollen availability.
Topics: Bees; Animals; Sterols; Lipid Metabolism; Metabolomics; Phytosterols; Crops, Agricultural; Fatty Acids; Mammals
PubMed: 37644282
DOI: 10.1007/s11306-023-02039-1 -
The American Journal of Clinical... Mar 2024Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD.
OBJECTIVES
To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD.
METHODS
In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed.
RESULTS
In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss.
CONCLUSION
Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome.
TRIAL REGISTRATION NUMBER
This trial was registered at the clinicaltrials.gov as NCT05259475.
Topics: Female; Humans; Non-alcoholic Fatty Liver Disease; Diet, Mediterranean; Liver; Weight Loss; Fatty Acids, Unsaturated; Cholesterol; Fatty Acids
PubMed: 38035997
DOI: 10.1016/j.ajcnut.2023.11.013 -
International Journal of Molecular... Jul 2023Bile acids (BAs) are well known to facilitate the absorption of dietary fat and fat-soluble molecules. These unique steroids also function by binding to the ubiquitous... (Review)
Review
Bile acids (BAs) are well known to facilitate the absorption of dietary fat and fat-soluble molecules. These unique steroids also function by binding to the ubiquitous cell membranes and nuclear receptors. As chemical signals in gut-liver axis, the presence of metabolic disorders such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and even tumors have been reported to be closely related to abnormal levels of BAs in the blood and fecal metabolites of patients. Thus, the gut microbiota interacting with BAs and altering BA metabolism are critical in the pathogenesis of numerous chronic diseases. This review intends to summarize the mechanistic links between metabolic disorders and BAs in gut-liver axis, and such stage-specific BA perturbation patterns may provide clues for developing new auxiliary diagnostic means.
Topics: Humans; Bile Acids and Salts; Diabetes Mellitus, Type 2; Liver; Non-alcoholic Fatty Liver Disease; Biomarkers
PubMed: 37569498
DOI: 10.3390/ijms241512123