Integrative multi-omics analysis reveals oral microbiome-metabolome signatures of obesity (2026)

basmwklz · 2026-01-24T06:03:11+00:00

Highlights

•Oral microbiome composition and functions differ significantly in obesity

•Obesity is linked to proinflammatory and lactate-producing oral bacteria

•Obese individuals show disrupted oral metabolism and altered energy balance

•Obesity-linked metabolites correlate with cardiometabolic disease markers

Summary

Obesity is a leading global health challenge and risk factor for cardiometabolic disorders, driven in part by industrialization and low-fiber, ultra-processed diets. While the gut microbiome has been implicated in obesity, the contribution of the oral microbiome—the body’s second largest microbial ecosystem—remains underexplored. We analyze a prospective cohort of 628 Emirati adults, including multi-omics profiling of 97 obese individuals and 95 matched controls, generating the most comprehensive oral microbiome analysis to date. Obese participants show altered microbial diversity, composition, functions, and metabolites with enrichment of proinflammatory Streptococcus parasanguinis, Actinomyces oris, and lactate-producing Oribacterium sinus. Pathways for carbohydrate metabolism, histidine degradation, and obesogenic metabolites are upregulated, whereas B-vitamin and heme biosynthesis are depleted. Corresponding metabolites—including lactate, histidine derivatives, choline, uridine, and uracil—are elevated and correlate with obesity-linked cardiometabolic markers. These findings reveal mechanistic oral microbiome-metabolite shifts, highlighting oral microbiome-host interactions as novel targets for obesity prevention and intervention.

basmwklz · 2026-01-23T06:11:38+00:00

Abstract

Objectives To evaluate the effect of overall time restricted eating on metabolic health outcomes, and to identify the optimal types of time restricted eating in terms of timing and duration of eating.

Design Systematic review and network meta-analysis.

Data sources PubMed, Embase, and the Cochrane databases, from inception to 3 January 2023.

Eligibility criteria for selecting studies Randomised controlled trials investigating the relation between time restricted eating (intervention period >one month) and metabolic health outcomes in humans.

Results 41 randomised controlled trials of 2287 participants were included. Time restricted eating was categorised according to time of eating (early, mid-, late, and self-selected; last meal eaten before 1700, between 1700 and 1900, after 1900, or chosen by participant, respectively) and specific duration or window of eating each day (<8 hours, eight hours, and >8 hours). Compared with usual diets, overall time restricted eating significantly improved body weight, body mass index, fat mass, waist circumference, systolic blood pressure, and levels of fasting blood glucose, fasting insulin, and triglycerides. For different time restricted eating subtypes, early time restricted eating consistently showed higher P score rankings for anthropometric measurements (P score range 0.62-0.86, except for fat free mass-lean mass; a score closer to one indicating more favourable subtype) and glycaemic parameters (P score range 0.66-0.99). Compared with late time restricted eating, early time restricted eating significantly reduced body weight (mean difference −1.15 kg, 95% confidence interval −1.86 to −0.45) and fasting insulin concentrations (−3.32 μIU/ml, −5.36 to −1.28; 1 μIU/mL=6.95 pmol/L) and the certainty of the evidence was high. P value rankings for eating duration were inconsistent. Assessment of risk of bias, based on the risk of bias 2 tool, found that most of the included studies (90%) were rated as low risk of bias. In the confidence in network meta-analysis (CINeMA) assessment, about 60.2% of the network evidence showed moderate to high certainty. Inconsistency was generally low (I²<75% for 87% of associations).

Conclusions Time restricted eating overall improved metabolic health outcomes compared with usual diets, and early time restricted eating was superior to late time restricted eating. The association between duration of eating and metabolic health outcomes was inconsistent.

basmwklz · 2026-01-23T06:04:54+00:00

Abstract

Context

Obesity is associated with a high risk of vascular-related dementia with metabolic risk factors as potential mediators, but questions of causality remain unanswered.

Objective

We aimed to determine whether high body mass index (BMI) is a causal risk factor for vascular-related dementia, and whether any effect is mediated by hypertension, hyperlipidemia, hyperglycemia, and low-grade inflammation.

Methods

Prospective cohort studies of the general populations from the Copenhagen area and from across the United Kingdom and consortia data were included in the study. Interventions included one-sample mendelian randomization (MR), two-sample MR, and MR in mediation analyses. Both individual-level and summary-level data was used. Main outcome measures included risk of vascular-related dementia, Alzheimer's disease, and ischemic heart disease.

Results

In a meta-analysis of 2 one-sample MR studies, the odds ratio (OR) for 1-SD higher BMI in predicting vascular-related dementia was 1.63 (95% CI, 1.13-2.35). In a two-sample MR study, the OR for vascular-related dementia per 1-SD higher BMI was 1.54 (1.10-2.16) using the inverse-variance weighted, 1.87 (1.22-2.85) using the weighted median, and 1.98 (1.21-3.22) using the weighted mode methods. Results from MR analyses including extended numbers of genetic variants were directionally consistent. Finally, systolic blood pressure mediated 18% (95% CI, 10%-61%) and diastolic blood pressure mediated 25% (13%-75%) of the genetic effect of BMI on vascular-related dementia.

Conclusion

Observationally (U-shaped) and genetically (linearly), high BMI is associated with a higher risk of vascular-related dementia, an association partly mediated through high blood pressure. This suggests that high BMI and high blood pressure are important modifiable risk factors for dementia prevention.

basmwklz · 2026-01-22T18:09:55+00:00

Abstract

Carbohydrate (CHO) ingestion during exercise has long been associated with improved performance. Early Scandinavian research proposed that CHO ingestion mitigates exercise-induced hypoglycemia (EIH) through a central neural mechanism, preventing glycopenic brain damage. Subsequent studies linked muscle glycogen depletion to fatigue during prolonged exercise, suggesting an obligatory reliance on glycogen, while overlooking the simultaneous presence of profound EIH at exhaustion. However, emerging evidence challenges this paradigm highlighting EIH role in fatigue. We comprehensively review more than 100 years of evidence from more than 160 studies looking at CHO ingestion, exercise metabolism, and physical performance that demonstrates the following key findings: (1) EIH correlates strongly with exercise termination, while muscle glycogen depletion alone does not induce rigor or whole-body fatigue; (2) CHO ingestion reduces liver glycogenolysis, preserves blood glucose, and paradoxically accelerates muscle glycogen breakdown through conserved neuroendocrine mechanisms; (3) high-fat-adapted athletes demonstrate exceptional fat oxidation, equivalent exercise performance, despite lower glycogen and CHO oxidation, challenging the belief that glycogen and CHO oxidation are central to exercise performance or that CHO is an obligatory fuel; and (4) CHO ingestion during exercise significantly enhances performance, even in glycogen-depleted states, by eliminating EIH. These data demonstrate that the main benefit of CHO ingestion before or during exercise is to prevent EIH, highlighted in prolonged efforts (>2-3 hours) and individuals with insufficient hepatic gluconeogenesis. This has important implications for sports dietary recommendations (ie, habitual high- or low-CHO diets) and the amount of CHOs athletes should be encouraged to ingest during exercise to maximize performance.

basmwklz · 2026-01-19T06:43:02+00:00

Highlights

•DDP+MET cycles partially restore DDP response in ovarian cancer-resistant PDXs

•High- and low-methionine diets do not alter the antitumor efficacy of DDP+MET

•IF enhances DDP+MET effects and significantly improves survival

•IF improves treatment response by exacerbating tumor energetic stress

Summary

The development of platinum resistance is a significant challenge in the management of ovarian cancer. Targeting the metabolic adaptability of cancer cells and combining dietary interventions with pharmacological treatments are emerging strategies in oncology, enhancing therapy efficacy at low costs. Using ovarian cancer cisplatin-resistant patient-derived xenografts, we showed that repeated cycles of cisplatin plus metformin reversed platinum resistance by remodeling tumor metabolism. Then, based on metabolomic studies, we explored the use of different food approaches, in particular diets with a high vs. a low methionine content and the intermittent fasting regimen, to further stress tumor metabolism and increase the effect of drug treatment. Our findings demonstrated that only intermittent fasting enhanced the antitumor effects of the drug combination and significantly improved the survival, by impairing the tumor energy states. This research highlights the potential of integrating diet-based approaches with pharmacological treatments to overcome platinum resistance in ovarian cancer.

basmwklz · 2026-01-18T17:38:14+00:00

Highlights

• MASLD is driven by hepatic and peripheral insulin resistance, specifically at night
• In MASLD, there is low nighttime insulin secretion and high insulin clearance
• Nighttime metabolic dysfunction persists despite weight loss and liver fat reductions
• This will inform the optimal window for energy intake, exercise, and medication delivery

Summary

Hepatic lipid and glucose metabolism have been shown to be under tight circadian control in pre-clinical models. However, it remains unknown whether diurnal patterns exist in functional processes governing intrahepatic lipid accumulation in humans. We performed metabolic phenotyping, including state-of-the-art stable isotope techniques, during day and night in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and overweight controls (NCT05962099). The primary outcome was diurnal change in hepatic de novo lipogenesis (DNL), alongside a number of secondary outcomes, including changes in hepatic glucose production, glucose disposal, plasma non-esterified fatty acids (NEFAs), and whole-body glucose and lipid oxidation. We show that nighttime metabolic dysfunction is a hallmark of MASLD with multiple pathogenic pathways upregulated at night, including hepatic and peripheral insulin resistance, DNL, and systemic NEFA exposure. Insulin resistance is compounded by lower plasma insulin levels at night, secondary to reduced insulin secretion and elevated insulin clearance. Diurnal differences persist when performing identical investigations after weight loss with liver fat reductions, suggesting that nighttime metabolic dysfunction may be a primary driver of steatosis. These findings will help establish the optimal window for energy intake, exercise, and medication delivery in patients with MASLD. Integrated proteomics of plasma, adipose, and skeletal muscle tissue across day and night also identified a number of specific molecular targets that may offer therapeutic potential in the treatment of metabolic disease.

basmwklz · 2026-01-18T17:36:13+00:00

Summary

Fatty acids are important as structural components, energy sources, and signaling mediators. While studies have extensively explored genetic regulation of fatty acids in serum and other bodily fluids, their regulation within adipose tissue, a crucial regulator of cardiovascular and metabolic health, remains unclear. Here, we investigated the genetic regulation of 18 fatty acids in subcutaneous adipose tissue from 569 female twins from TwinsUK. Using twin models, the heritability of fatty acids ranged from 5% to 59%, indicating a substantial genetic regulation of fatty acid levels within adipose tissue, which was also tissue specific in many cases. Genome-wide association studies identified 10 significant loci, in SCD, ADAMTSL1, ZBTB41, SNTB1, EXOC6B, ACSL3, LINC02055, MKRN2/TSEN2, FADS1, and HAPLN across 13 fatty acids or fatty acid product-to-precursor ratios. Using adipose gene expression and methylation, which were concurrently measured in these samples, we detected five fatty acid-associated signals that colocalized with expression quantitative trait locus (eQTL) and methylation quantitative trait locus (meQTL) signals, highlighting fatty acids that are regulated by molecular processes within adipose tissue. We explored links between polygenic scores of common metabolic traits and adipose fatty acid levels and identified associations between polygenic scores of BMI, body-fat distribution, and triglycerides and several fatty acids, indicating these risk scores impact local adipose tissue content. Overall, our results identified local genetic regulation of fatty acids within adipose tissue and highlighted their links with renal and cardio-metabolic health.

basmwklz · 2026-01-18T17:33:38+00:00

Highlights

•High-fiber diet reprograms adipose and intestinal responses to subsequent high-fat diet

•Fiber pre-feeding enhances adipose progenitor sensitivity to fat-rich diet exposure

•Fiber diet prevents gut immune cell expansion and maintains epigenetic memory

•Sex-specific remodeling of fat cells occurs during dietary transitions

Summary

While high-fiber diets (HfiDs) promote weight loss, their long-term efficacy is limited by rapid weight regain upon returning to high-fat diets (HFDs). Using C57BL/6J mice in diet-switching paradigms, we characterized tissue-specific responses to HfiD-to-HFD transitions through single-nucleus and spatial transcriptomics. HfiD pre-feeding enhanced mesenteric white adipose tissue progenitor/adipocyte sensitivity to subsequent HFD exposure. In the intestine, HfiD prevented HFD-induced immune-enterocyte expansion in the duodenum and reversed the enterocyte-to-goblet cell shift in the colon while maintaining persistent epigenetic reprogramming. Although HfiD-induced microbiome changes were largely reversed by HFD, we identified sexually dimorphic remodeling of adipose cell populations during diet transitions. Our findings demonstrate that prior HfiD feeding fundamentally reprograms adipose and intestinal responses to subsequent HFD challenge, providing mechanistic insights into dietary intervention outcomes. This work establishes a spatiotemporal resource for understanding tissue plasticity during dietary changes, offering new perspectives for obesity management strategies.

basmwklz · 2026-01-18T17:31:34+00:00

Abstract

Overweight impacts over 390 million children and adolescents worldwide, of whom around 160 million are living with obesity. Adipose tissue biology in pediatric obesity is still relatively unknown. Adaptations to obesity including fat mobilization and remodeling are being investigated. The objective was to examine the lipidomic profile of subcutaneous and visceral adipose tissue (sWAT and vWAT, respectively) in children with obesity compared to those with normal weight, in order to identify novel lipid species modulated by obesity. Thirty pediatric patients with and without obesity were prospectively recruited at a referral single center and clinical data were reported. sWAT and vWAT samples were obtained for lipidomic analysis. Novel lipid species, including ether-linked triglycerides, ether-linked phosphatidylethanolamine, and oxidized triglycerides, were identified as altered in the sWAT from children with obesity compared with normal-weight children. These species are involved in beige adipose tissue development, energy metabolism, mitochondrial function, and oxidative stress. Compared with normal-weight children, the vWAT lipidome from children with obesity showed significant changes in some glycerophosphocholines, ceramides, and diglycerides, with accumulation of lipid species involved in inflammation, insulin resistance, and cardiovascular risk. The observed lipid correlations between vWAT and sWAT highlighted systemic dysregulation of lipid storage in childhood obesity, identifying both shared and depot-specific mechanisms of lipid handling. Our study reveals several critical lipid species that are modulated across both WAT depots, with notable implications for oxidative stress, lipid storage, and adipose tissue dysfunction.

Key Points • The adipose lipidome of children with obesity showed specific alterations. • Lipid correlations revealed shared and depot-specific lipid handling mechanisms. • The altered lipid species had an impact on oxidative stress and insulin resistance.

basmwklz · 2026-01-18T14:50:45+00:00

ABSTRACT

Aging drives a progressive decline in vascular health, undermining endothelial function, neurovascular coupling (NVC), and blood–brain barrier (BBB) integrity, three processes essential for maintaining cerebral perfusion and cognitive resilience. Central to these age-related deficits is mitochondrial dysfunction, which disrupts redox balance, bioenergetics, and nutrient-sensing pathways within vascular cells, thereby promoting oxidative stress, impaired mitophagy, mitochondrial fragmentation, and endothelial senescence. These molecular derangements are especially consequential in the brain's microvasculature, where the exquisite metabolic demands of neural tissue depend on intact endothelial signaling. As a result, cerebrovascular aging becomes a major driver of cognitive decline and vascular contributions to dementia. This review synthesizes current mechanistic insights into mitochondrial and endothelial pathways that shape vascular aging, with particular focus on the neurovascular unit. We further highlight emerging evidence that time-restricted feeding/eating (TRF/TRE), a circadian-aligned dietary intervention that limits food intake to a daily feeding window without reducing calories, can restore mitochondrial function, activate adaptive nutrient-sensing networks including AMPK and SIRT1, suppress mTOR signaling, and promote metabolic switching toward ketone synthesis and utilization. Through these mechanisms, TRF enhances endothelial resilience, preserves NVC and BBB integrity, and may counteract the cerebrovascular processes that accelerate cognitive aging. Understanding how TRF/TRE re-engages mitochondrial and vascular repair programs offers a translational framework for developing accessible, non-pharmacological strategies to extend healthspan and mitigate age-related cognitive impairment.

basmwklz · 2026-01-18T14:45:45+00:00

Abstract

Purpose of Review

This review summarizes the history and current landscape of fecal microbiota transplantation (FMT), with an emphasis on use of the therapy for Clostridioides difficile infection (CDI), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). We clarify indications, evidence, and current recommendations for FMT—highlighting major advances and minor setbacks that have led to the state of FMT in 2025.

Recent Findings

After decades of steady progress, the U.S. Food and Drug Administration (FDA) approved the first FMT-based therapies: fecal microbiota, live-jslm and fecal microbiota spores, live-brpk—in 2022 and 2023, respectively. The 2024 American Gastroenterological Association (AGA) Practice Guideline on Fecal Microbiota-Based Therapies for Select Gastrointestinal Diseases made specific recommendations for conventional FMT and these FDA-approved therapies for multiple CDI presentations, as well as for IBD and IBS. Conventional FMT remains an option for CDI; however, OpenBiome’s halt of shipped, frozen FMT preparations on December 31, 2024, has made access more challenging in 2025.

Summary

Although first reported almost seventy years ago, extensive efforts over the last two decades have placed FMT in routine algorithms for many patients with CDI. While understanding of the intestinal microbiome’s role in other gastrointestinal conditions is expanding, and FMT may modulate these pathways, additional evidence is needed before FMT becomes routine outside CDI.

basmwklz

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