Background: Branched-chain amino acids (BCAAs) are essential amino acids for protein metabolism. Preclinical research in mice suggested that BCAA intake relative to other amino acids, in the context of a high-carbohydrate diet, was associated with hyperphagia, obesity, and reduced lifespan. These effects were not attributed to BCAAs alone, nor did they manifest through canonical mechanistic target of rapamycin-insulin-like growth factor 1 pathways; rather, they resulted from indirect effects of other amino acids, notably tryptophan, on appetite. As population aging and obesity-related chronic diseases present significant public health challenges, understanding appetite regulation is critical. To date, no clinical trial has examined the effects of BCAAs on appetite regulation in older adults. On the basis of our preclinical results, we hypothesized that, compared to the control diet, a diet supplemented either with BCAA or with BCAAs and methionine would increase appetite and energy intake, whereas supplementation with BCAA and tryptophan would not increase appetite. Objective: We aimed to translate these preclinical findings to humans by examining the effects of BCAAs per se and in combination with tryptophan and methionine on appetite and other health measures in a cohort of older participants. Methods: This randomized controlled clinical trial recruited 110 adults (aged 65-80 y; BMI 20-35 kg/m2). Participants were randomly allocated to four 4-week intervention groups: (1) control (no supplementation), (2) BCAAs, (3) BCAAs+tryptophan, or (4) BCAAs+methionine. All participants received a controlled diet, with intervention groups additionally receiving amino acid supplements. The primary outcomes are appetite assessed via self-reports and fibroblast growth factor 21 levels (a marker of protein appetite), and energy intake quantified from dietary intake data. Secondary outcomes include body composition, cardiometabolic health, gut microbiota, blood biomarkers, sleep, and physical performance. Descriptive statistics will be used to summarize participant characteristics. Linear mixed models will assess intervention effects, with and without adjustment for relevant covariates. Diet-specific self-reported appetite and palatability scores will be analyzed using generalized additive mixed models. Results: The trial was registered on April 12, 2021. Recruitment commenced in April 2022 and was completed in November 2025, with 308 individuals screened and 100 completing the study. Data analyses are planned for completion by December 2026, with results expected to be published in 2027. Data cleaning and analysis are currently in progress and are expected to be completed by December 2026, with trial results expected to be published in 2027. Conclusions: This study will clarify the effects of BCAAs, either alone or in combination with tryptophan or methionine, on appetite and related outcomes in an older population. The findings may inform nutritional strategies targeting appetite regulation and metabolic health to support healthy aging.

BACKGROUND:Diet is associated with major adverse cardiovascular events (MACE). OBJECTIVE:We evaluated the associations between empirically derived dietary patterns and MACE. DESIGN:Prospective cohort study. SETTING:The Concord Health and Ageing in Men Project, Sydney, Australia. PARTICIPANTS:539 community-dwelling older Australian men aged 75 years and older. METHODS:Men underwent dietary assessment using a validated dietitian-administered diet history questionnaire. Cox regression analyses were conducted between MACE and the three dietary patterns identified from factor analysis. Five-point MACE comprised of all-cause mortality, myocardial infarction (MI), congestive cardiac failure (CCF), coronary revascularisation, and/or ischaemic stroke. Four-point MACE included the four endpoints of MI, CCF, coronary revascularisation, and/or ischaemic stroke, and excluded all-cause mortality. RESULTS:At a median of 5.3 (IQR 4.6-6.3) years of follow-up, the incidences were: five-point MACE 31.2% (n = 168); four-point MACE excluding all-cause mortality 17.8% (n = 96); all-cause mortality 20.1% (n = 111); CCF 11.3% (n = 61); MI 3.7% (n = 20); stroke 3.2% (n = 17); and coronary revascularisation 3.1% (n = 15). In fully adjusted analyses, compared to the bottom tertile, the middle tertile of 'vegetables-legumes-seafood' dietary pattern was associated with reduced five-point MACE (HR 0.67 [95% CI: 0.45, 0.99, P = .047]), and CCF (HR 0.31 [95% CI: 0.15, 0.65, P = .002]), whilst the middle tertile of 'wholegrains-milk-other fruits' dietary pattern was associated with increased five-point MACE (HR 1.78 [95% CI: 1.17, 2.70, P = .007]), four-point MACE (HR 1.92 [95% CI: 1.12, 3.30, P = .018]), and CCF (HR 2.33 [95% CI: 1.17, 4.65, P = .016]). For the 'discretionary-starchy vegetables-processed meats' dietary pattern, a higher score was associated with increased five-point MACE (HR 1.33 [95% CI: 1.09, 1.62, P = .004]), and all-cause mortality (HR 1.63 [95% CI: 1.26, 2.12, P < .001]), and compared to the bottom tertile, the top tertile was associated with increased all-cause mortality (HR 2.26 [95% CI: 1.27, 4.00, P = .005]). CONCLUSION:Older men may benefit from consuming a 'vegetables-legumes-seafood' dietary pattern rather than 'discretionary-starchy vegetables-processed meats' and 'wholegrains-milk-other fruits' dietary patterns for the prevention of MACE.

The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance. However, unsupervised human protein-based clustering analysis revealed two distinct CVD risk clusters (low-risk and high-risk) with different blood pressure (by 9 mmHg) and sex-dependent dietary potassium and fiber intake. In the human proteome, the low-risk group had lower angiotensin-converting enzymes, inflammatory proteins associated with neutrophil extracellular trap formation and auto-immune diseases. In the microbial proteome, the low-risk group had higher expression of phosphate acetyltransferase that produces SCFAs, particularly in fiber-fermenting bacteria. This model identified severity across phenotypes in heart failure patients and long-term risk of cardiovascular events in a large population-based cohort. These findings underscore multifactorial gut-to-host mechanisms that may underlie risk factors for CVD.

Plant-based diets reduces the risk of chronic conditions. The interaction between protein source and other macronutrients-fat (F) and carbohydrate (C)-has yet to be investigated. The aim was to assess the main and interactive effects of protein-source (plant vs. animal) and F:C (high or low) and the transition from an Australian diet to a whole food diet on various health markers in older individuals. This single-blinded, parallel, randomised experimental trial used a 2 × 2 factorial design to compare pro-vegetarian (70:30 plant to animal) versus omnivorous (50:50 plant to animal) diets at 14% protein and varying fat-to-carbohydrate ratios (high fat ~40% vs. low fat ~30%) over 4 weeks. Study foods were provided, alcohol consumption was discouraged, and dietary intake was determined through food records. Analysis included both RCT and observational data. Changes in appetite, palatability of diets, and dietary intake were assessed. Body composition, muscle strength, function, gut microbiome, and cardiometabolic health parameters were measured. Data from 113 (of the 128 randomised) individuals aged 65-75 years were analysed. Pro-vegetarian diets reduced diastolic blood pressure, total cholesterol and glucose levels. Moreover, the overall sample exhibited increased short-chain fatty acids and FGF21 levels, as well as improvements in body composition, function, and cardio-metabolic parameters irrespective of dietary treatment. Transitioning to a diet rich in fruit, vegetables, fibre, and moderate protein was associated with improved health markers in older age, with added benefits from pro-vegetarian diets. Further research on long-term effects is needed.

Our objective was to evaluate the association of antioxidant intake and the inflammatory potential of the diet with functional decline in older men. A diet history questionnaire was used to collect dietary intake data from men aged ≥ 75 years (n 794) participating in the Concord Health and Aging in Men Project cohort study. Intake of vitamins A, C, E and Zn were compared with the Australian Nutrient Reference Values to determine adequacy. The Energy-adjusted Dietary Inflammatory Index (E-DIITM) was used to assess the inflammatory potential of the diet. Physical performance data were collected via handgrip strength and walking speed tests, and activities of daily living (ADL) and instrumental activities of daily living (IADL) questionnaires, at baseline and 3-year follow-up (n 616). Logistic regression analysis was used to identify associations between diet and incident poor physical function and disability. Both poor antioxidant intake and high E-DII scores at baseline were significantly associated with poor grip strength and ADL disability at 3-year follow-up. No significant associations with walking speed or IADL disability were observed. Individual micronutrient analysis revealed a significant association between the lowest two quartiles of vitamin C intake and poor grip strength. The lowest quartiles of intake for vitamins A, C, E and Zn were significantly associated with incident ADL disability. The study observed that poor antioxidant and anti-inflammatory food intake were associated with odds of developing disability and declining muscle strength in older men. Further interventional research is necessary to clarify the causality of these associations.

Background: Diet may be associated with frailty. Objective: We aimed to evaluate the associations between empirically derived dietary patterns and frailty in older men. Design: Prospective cohort study. Setting: The Concord Health and Ageing in Men Project, Sydney, Australia. Participants: 785 community-dwelling older Australian men aged 75 years and older. Methods: Men underwent dietary assessment using a validated dietitian-administered diet history questionnaire. Factor analysis identified three dietary patterns. Multinomial logistic regression was conducted between frailty and dietary patterns for cross-sectional analyses and longitudinal analyses over a 3-year follow-up. Frailty was defined by the Fried frailty phenotype. Results: Of the 785 men, pre-frailty was prevalent in 47.1% (n = 370), and frailty in 8.3% (n = 65). In fully adjusted cross-sectional analyses, the top tertile and a higher ‘vegetables-legumes-seafood’ dietary pattern score were associated with reduced prevalence of frailty (OR 0.34 [95% CI: 0.12, 0.93, P = .036]) and OR 0.50 [95% CI: 0.30, 0.83, P = .007] respectively). The top tertile of the ‘discretionary-starchy vegetables-processed meats’ dietary pattern was also associated cross-sectionally with increased prevalence of pre-frailty (OR 1.75 [95% CI: 1.08, 2.83, P = .022]). Of the 296 robust men in fully adjusted longitudinal analyses, the incidence of pre-frailty was 52.4% (n = 155), and frailty was 5.4% (n = 16) over a 3-year follow-up. The middle tertile of the ‘vegetables-legumes-seafood’ dietary pattern had a non-significant trend towards reduced incident pre-frailty (OR 0.52 [95% CI: 0.27, 1.00, P = .050]). Conclusion: Consumption of a ‘vegetables-legumes-seafood’ dietary pattern appears to be less favoured by frail older men.

OBJECTIVE:Exposure in utero to maternal diet can program offspring health and susceptibility to disease. Using C57BL6/JArc mice, we investigated how maternal dietary protein to carbohydrate balance influences male and female offspring appetite and metabolic health. METHODS:Dams were placed on either a low-protein (LP) or high-protein (HP) diet. Male and female offspring were placed on a food choice experiment post weaning and were then constrained to either a standard diet or Western diet. Food intake, body weight, and composition were measured, and various metabolic tests were performed at different timepoints. RESULTS:Offspring from mothers fed HP diets selected a higher protein intake and had increased body weight in early life relative to offspring from LP diet-fed dams. As predicted by protein leverage theory, higher protein intake targets led to increased food intake when offspring were placed on no-choice diets, resulting in greater body weight and fat mass. The combination of an HP maternal diet and a Western diet further exacerbated this obesity phenotype and led to long-term consequences for body composition and metabolism. CONCLUSIONS:This work could help explain the association between elevated protein intake in humans during early life and increased risk of obesity in childhood and later life.

Background/Objective: The gut microbiota is a crucial link between diet and cardiovascular health by producing beneficial metabolites, such as short-chain fatty acids (SCFAs), through fibre fermentation. However, most studies have focused on microbial DNA to infer microbiota function. Here, we employed metaproteomics, a novel method to capture gut human and microbiota protein expression profiles concurrently. We aimed to investigate the crosstalk between gut microbiota, diet, host gut health, and blood pressure (BP). Methods: Mass spectrometry-based metaproteomic analysis was performed on 61 faecal samples with paired ambulatory BP monitoring, food intake (food frequency questionnaire), and demographic data. Results: We identified 21,594 microbial and 1,072 human proteins. Traditional risk factors (age, BMI, sex, BP) explained only ∼10% of the proteome variance. However, unsupervised clustering analysis of both human and microbial proteome revealed two distinct clusters (low-risk and high-risk) with significantly different 24-hour systolic BP (mean±SD, low-risk 116±13mmHg vs high-risk: 126±15mmHg, P=0.016), women prevalence (72.4% vs 40.6%, P=0.025), and diet quality (assessed as Athlete Diet Index, 61.6±6.7 vs 57.8±7.6, P=0.044). In the human proteome, the low-risk group had lower expression of the VEGFA-VEGFR2 signalling pathway and tight junction proteins and higher SCFA production (particularly propionate), suggesting an anti-inflammatory gut environment. In the microbial proteome, the low-risk group had higher activity of inorganic ion transport and metabolism-related proteins, with increased expression of acetate kinase that produces both the SCFAs acetate and propionate, particularly in primary fibre-fermenting bacteria, including Phocaeicola dorei and Blautia wexlerae. Finally, via co-expression networks, we identified profilin-1 (PFN1), which contributes to hypertension and atherosclerosis, as a crucial human protein associated with several bacteria present in the high-risk group. Conclusions: Employing an unsupervised clustering based on human and microbial proteomics, we identified two groups of participants with varying traditional and emerging cardiovascular risk factors. This was explained by complex interactions among diet, gut microbiota, and BP. This underscores the need for sophisticated models to understand multifactorial risk factors for cardiovascular disease.

Objective: Diets with a low proportion of energy from protein have shown to cause overconsumption of non-protein energy, known as Protein Leverage. Older adults are susceptible to nutritional inadequacy. The aim was to investigate associations between protein to non-protein ratio (P:NP) and intakes of dietary components and assess the nutritional adequacy of individuals aged 65-75 years from the Nutrition for Healthy Living (NHL) Study. Design: Cross-sectional. Nutritional intakes from seven-day weighed food records were compared with the Nutrient Reference Values for Australia and New Zealand, Australian Guide to Healthy Eating, Australian Dietary Guidelines and World Health Organisation Free Sugar Guidelines. Associations between P:NP and intakes of dietary components were assessed through linear regression analyses. Setting: NHL Study. Participants: 113 participants. Results: Eighty-eight (59 female and 29 male) with plausible dietary data had a median (interquartile range) age of 69 years (67-71), high education level (86 %) and sources of income apart from the age pension (81 %). Substantial proportions had intakes below recommendations for dairy and alternatives (89 %), wholegrain (89 %) and simultaneously exceeded recommendations for discretionary foods (100 %) and saturated fat (92 %). In adjusted analyses, P:NP (per 1 % increment) was associated with lower intakes of energy, saturated fat, free sugar and discretionary foods and higher intakes of vitamin B12, Zn, meat and alternatives, red meat, poultry and wholegrain % (all P < 0 center dot 05). Conclusions: Higher P:NP was associated with lower intakes of energy, saturated fat, free sugar and discretionary. Our study revealed substantial nutritional inadequacy in this group of higher socio-economic individuals aged 65-75 years.

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 A(1c) (HbA(1c)), 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, HbA(1c) 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, HbA(1c), and body weight by 6.6mg/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 (-0.1mmHg; 95% CI, -2.8 to 2.6). The GRADE assessment showed a moderate level of evidence for LDL-C and HbA(1c) 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.

Dietary fiber plays a crucial role in maintaining gut and overall health. The objective of this study was to investigate whether different types of dietary fiber elicited specific changes in gut microbiota composition and the production of short-chain fatty acids. To test this, a longitudinal crossover study design was employed, in which healthy adult women consumed three distinct dietary fiber supplements: Inulin (fructo-oligosaccharide), Vitafiber (isomalto-oligosaccharide), and Fibremax (mixture of different fiber) during a one-week intervention period, followed by a 2-week washout period. A total of 15 g of soluble fiber was consumed daily for each supplement. Samples were collected before and after each intervention to analyze the composition of the gut microbiota by 16S rRNA sequencing and fecal levels of short-chain fatty acids measured using nuclear magnetic resonance. Phenotypic changes in peripheral blood mononuclear cells were studied in subsets of participants with higher SCFA levels post-intervention using spectral flow cytometry. The results revealed substantial stability and resilience of the overall gut bacterial community toward fiber-induced changes. However, each supplement had specific effects on gut bacterial alpha and beta diversity, SCFA production, and immune changes. Inulin consistently exerted the most pronounced effect across individuals and certain taxa were identified as potential indicators of SCFA production in response to inulin supplementation. This distinguishing feature was not observed for the other fiber supplements. Further large-scale studies are required to confirm these findings. Overall, our study implies that personalized dietary fiber intervention could be tailored to promote the growth of beneficial bacteria to maximize SCFA production and associated health benefits.

IMPORTANCE: The evidence that maintaining a healthy body weight in conjunction with healthier eating patterns, exercise training, and reduced stress can improve clinical outcomes in patients with atherosclerotic cardiovascular disease is substantial. However, little is known about the magnitude and temporal effects of a comprehensive lifestyle treatment on coronary artery anatomy, myocardial inflammation, and fibrosis in people affected by coronary heart disease. OBJECTIVE: To conduct a randomised clinical trial to determine the impact of a 12-month intense lifestyle intervention delivered via an mHealth platform (in the form of a mobile App) versus standard clinical care on low attenuation plaque volume and structure, stress myocardial perfusion, and diastolic function. DESIGN: A single centre, parallel-group, randomised controlled trial. The co-primary endpoints are: 1-Low Attenuation Plaque (LAP) volume (mm3) using coronary computed tomography angiography (CCTA) at 12 months, and 2-Adenosine stress myocardial blood flow (stress MBF, mL/min/g) using cardiovascular magnetic resonance imaging (MRI) at 12 months. Other key measurements include liver steatosis by MRI, subclinical abnormalities detected by advanced electrocardiography, arterial stiffness, endothelial function, genomic, metabolomic, and gut microbiome-related adaptations to these structural changes. An intention-to-treat principle will be used for all analyses. SETTING: Participants will be recruited from a large academic cardiology office practice (Central Sydney Cardiology) and Royal Prince Alfred Hospital (RPAH) Departments of Cardiology and Radiology. All clinical investigations will be undertaken within the Charles Perkins Centre-RPAH clinic. PARTICIPANTS: Individuals (n = 150) with stable coronary heart disease who have low attenuation plaque based on a CCTA within the past 3 months, will be randomised to a lifestyle intervention program comprising a 5:2 pesco-vegetarian diet, exercise training, and mindfulness-based stress reduction (n = 75) or usual care (n = 75). DISCUSSION: This trial will represent the single most detailed and integrated analysis of the effects of a comprehensive lifestyle intervention targeting multiple metabolic pathways, delivered via a customized mHealth App on smart devices, on coronary macro- and microcirculation, heart physiology, and cardiometabolic risk. It will provide a new framework for allowing clinicians and individuals to optimise metabolic health for the prevention and management of atherosclerotic cardiovascular diseases that is epidemic in modern society.

Objective: To quantify the full life cycle impacts of ultra-processed foods (UPF) for key environmental, economic and nutritional indicators to identify trade-offs between UPF contribution to broad-scope sustainability.Design: Using 24-h dietary recalls along with an input-output database for the Australian economy, dietary environmental and economic impacts were quantified in this national representative cross-sectional analysis. Food items were classified into non-UPF and UPF using the NOVA system, and dietary energy contribution from non-UPF and UPF fractions in diets was estimated. Thereafter, associations between nutritional, environmental and economic impacts of non-UPF and UPF fractions of diets were examined using a multi-dimensional nutritional geometry representation.Setting: National Nutrition and Physical Activity Survey 2011-2012 of Australia.Participants: Respondents (n 5344) aged > 18 years with 1 d of 24-h dietary recall data excluding respondents with missing values and outlier data points and under reporters.Results: Australian diets rich in UPF were associated with reduced nutritional quality, high greenhouse gas emissions, energy use, and increased employment and income associated with the food supply chains. The environmental and economic impacts associated with the UPF portion of diets become more distinct when the diets are standardised to average protein recommendation.Conclusion: Increased consumption of UPF has socio-economic benefits, but this comes with adverse effects on the environment and public health. Consideration of such trade-offs is important in identifying policy and other mechanisms regarding UPF for establishing healthy and sustainable food systems.

AbstractBackgroundNutritional intake could influence the development of frailty. The aim was to evaluate the associations between dietary iron intakes and changes in dietary iron intakes with frailty.MethodsCross-sectional analyses involved 785 men with Fried frailty phenotype (FP) and 758 men with Rockwood frailty index (FI) data aged 75 years and older at nutrition assessment from the Concord Health and Ageing in Men Project prospective cohort study. Of these, 563 men who were FP robust or prefrail, and 432 men who were FI nonfrail were included in the longitudinal analyses for more than 3 years. Dietary intake was assessed at both timepoints using a validated diet history questionnaire. The dietary calculation was used to derive heme iron and nonheme iron intakes from total iron intakes. The associations were evaluated through binary logistic regression.ResultsIncidence of FP frailty was 15.3% (n = 86). In longitudinal analyses, maintaining total iron intakes (medium tertile −2.61–0.81 mg/d), increases in total iron and nonheme iron intakes (high tertiles ≥0.82 mg/d and ≥0.80 mg/d), and changes in nonheme iron intake (1 mg increment) were associated with reduced risks of incident FP frailty (OR: 0.47 [95% confindence interval (CI): 0.24, 0.93, p = .031], OR 0.48 [95% CI: 0.23, 0.99, p = .048], OR 0.41 [95% CI: 0.20, 0.88, p = .022], and OR 0.89 [95% CI: 0.82, 0.98, p = .017]).ConclusionMaintaining or increases in total dietary iron and increases or changes in dietary nonheme iron intakes more than 3 years were associated with reduced incidence of FP frailty in older men.

AIM The aim was to assess two macronutrient interventions in a 2x2 factorial dietary design to determine their effects on oral health. MATERIALS AND METHODS Participants (65-75 years old) with a BMI between 20-35 kg/m2 of a larger RCT who consented to an oral health assessment were recruited. They had ad libitum access to one of four experimental diets (omnivorous higher fat or higher carbohydrate, semi-vegetarian higher fat or higher carbohydrate) for 4 weeks. Periodontal examination included periodontal probing depth (PPD), clinical attachment level (CAL) and bleeding on probing. Oral plaque and gingival crevicular fluid (GCF) were collected before and after the intervention. RESULTS Between baseline and follow up the number of sites with a CAL <5 mm (mean difference (MD) -5.11±9.68, P=0.039) increased and the GCF amount (MD -23.42±39.42 Periotron Units (PU), P=0.050) decreased for the semi-vegetarian high fat diet. For the mean proportion of sites with PPD reduction >1 mm and CAL gain >1 mm significant differences were calculated between the diets investigated. The clinical parameters were not associated with changes of the oral microbiota. CONCLUSION The results of this study provided evidence that a semi-vegetarian higher fat diet provides benefits to clinical parameters of periodontal health. ACTRN12616001606471. This article is protected by copyright. All rights reserved.

Background: Blood pressure (BP) variability is an independent risk factor for cardiovascular events. Recent evidence supports a role for the gut microbiota in BP regulation. However, whether the gut microbiome is associated with BP variability is yet to be determined. Here, we aimed to investigate the interplay between the gut microbiome and their metabolites in relation to BP variability. Methods: Ambulatory BP monitoring was performed in 69 participants from Australia (55.1% women; mean±SD, 59.8±7.26 years; body mass index, 25.2±2.83 kg/m2). These data were used to determine nighttime dipping, morning BP surge (MBPS) and BP variability as SD. The gut microbiome was determined by 16S ribosomal RNA (rRNA) sequencing and metabolite levels by gas chromatography. Results: We identified specific taxa associated with systolic BP variability, nighttime dipping, and MBPS. Notably, Alistipesfinegoldii and Lactobacillus spp. were only present in participants within the normal ranges of BP variability, MBPS and dipping, while Prevotella spp. and Clostridium spp., were found to be present in extreme dippers and the highest quartiles of BP SD and MBPS. There was a negative association between MBPS and microbial α-diversity (r=−0.244, P=0.046). MBPS was also negatively associated with plasma levels of microbial metabolites called short-chain fatty acids (r=−0.305, P=0.020), particularly acetate (r=−0.311, P=0.017). Conclusions: Gut microbiome diversity, levels of microbial metabolites, and the bacteria Alistipesfinegoldii and Lactobacillus were associated with lower BP variability and Clostridium and Prevotella with higher BP variability. Thus, our findings suggest the gut microbiome and metabolites may be involved in the regulation of BP variability.

CONTEXT Cardiometabolic diseases are leading causes of death and morbidity. Aging increases the risk of disease development. Diet has protective and causal effects on cardiometabolic health. OBJECTIVE To consolidate the current evidence on the short- and long-term effects of dietary patterns on cardiometabolic health in adults aged ≥ 65 years. DATA SOURCES The Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Scopus, Global Health, and Pre-Medline databases, along with ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched. DATA EXTRACTION A total of 40 042 records were identified. Quality assessment involved using the revised Cochrane risk-of-bias tool for randomized trials and Joanna Briggs Institute checklists. The certainty of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS Thirteen articles were included (n = 5 cohort studies and n = 3 randomized controlled trials). The low-fat dietary pattern reduced adiposity; however, no effects were evident for hypertension incidence, composite coronary heart disease incidence (including myocardial infarction, coronary heart disease, and coronary revascularization), high-density lipoprotein cholesterol level, and increased blood pressure in the long term. The Mediterranean dietary pattern resulted in reduced triglyceride levels and systolic blood pressure, and had no effects on diastolic blood pressure and glucose in the short term. Other dietary patterns had inconclusive effects. CONCLUSIONS The Mediterranean dietary pattern showed the most benefits without harm on cardiometabolic health in older adults. The current body of evidence is small, indicating the need for more research to confirm these findings at a high certainty of evidence, and to include dietary patterns combined with other dietary components, subgroups with cardiometabolic disease or risk factors, longer follow-up, and outcomes that have not yet been investigated. Studies including these factors may help identify the most effective dietary pattern for cardiometabolic health benefits in older adults, to inform future guidelines. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42020141400.

The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae- dominated microbiomes than in Bacteroidaceae -dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline. Together, these data provide insight into the relevance of native gut microbiota signatures, dietary intake and systemic inflammation in shaping the response to and toxicity from ICIs, prompting the need for further studies in this area.

Background Risk factors for heart failure with preserved ejection fraction (HFpEF) include hypertension, age, sex, and obesity. Emerging evidence suggests that the gut microbiota independently contributes to each one of these risk factors, potentially mediated via gut microbial‐derived metabolites such as short‐chain fatty acids. In this study, we determined whether the gut microbiota were associated with HFpEF and its risk factors. Methods and Results We recruited 26 patients with HFpEF and 67 control participants from 2 independent communities. Patients with HFpEF were diagnosed by exercise right heart catheterization. We assessed the gut microbiome by bacterial 16S rRNA sequencing and food intake by the food frequency questionnaire. There was a significant difference in α‐diversity (eg, number of microbes) and β‐diversity (eg, type and abundance of microbes) between both cohorts of controls and patients with HFpEF (P=0.001). We did not find an association between β‐diversity and specific demographic or hemodynamic parameters or risk factors for HFpEF. The Firmicutes to Bacteroidetes ratio, a commonly used marker of gut dysbiosis, was lower, but not significantly so (P=0.093), in the patients with HFpEF. Compared with controls, the gut microbiome of patients with HFpEF was depleted of bacteria that are short‐chain fatty acid producers. Consistent with this, participants with HFpEF consumed less dietary fiber (17.6±7.7 versus 23.2±8.8 g/day; P=0.016). Conclusions We demonstrate key changes in the gut microbiota in patients with HFpEF, including the depletion of bacteria that generate metabolites known to be important for cardiovascular homeostasis. Further studies are required to validate the role of these gut microbiota and metabolites in the pathophysiology of HFpEF.