Biology subjects

Meadows, J.

Publications and source records attributed to Meadows, J..

5 recordsLinked to original sources

bioRxiv2026

Farnesoid X receptor-dependent microbiome-bile acid signaling mediates obstructive sleep apnea-induced atherosclerosis

Intermittent hypoxia and hypercapnia (IHC), a hallmark of obstructive sleep apnea (OSA), accelerates atherosclerosis, yet the underlying mechanisms remain unclear. The gut microbiota and metabolites, specifically bile acids, change with IHC and thus the bile acid receptor farnesoid X receptor (FXR) might mediate IHC-induced atherosclerosis. In this study, ApoE-/- and ApoE-/- FXR-/- mice were exposed to IHC or room air and fed with a high-fat, high-cholesterol diet for 10 weeks. Markers of atherosclerosis, fecal microbiome, and metabolome were then examined via Sudan IV staining, absolute abundance shotgun metagenomics, and untargeted liquid chromatography tandem mass spectrometry (LC-MS/MS). IHC markedly increased aortic atherosclerosis in ApoE-/-mice, an increase that was abolished by FXR deficiency. In addition, IHC reshaped gut microbial composition, promoting enrichment of bile acid-modifying taxa and increasing levels of microbial hydroxysteroid dehydrogenase (hsdh). The bile acid pool was also remodeled and associated with aortic atherosclerosis via FXR-dependent metabolic signals in ApoE-/- mice. Knockout of FXR disrupted microbiome shift under IHC and uncoupled microbial bile acid metabolism from vascular lesion development, thereby protecting against aortic atherosclerosis. These findings show that FXR has a central role in linking IHC, microbial bile acid metabolism, and cardiovascular pathology.

microbiology↗

bioRxiv2024

Gut Microbiota and Derived Metabolites Mediate Obstructive Sleep Apnea Induced Atherosclerosis

BackgroundObstructive sleep apnea (OSA) is characterized by intermittent hypoxia/hypercapnia (IHC), affects predominantly obese individuals, and increases atherosclerosis risk. Since we and others have implicated gut microbiota and metabolites in atherogenesis, we dissected their contributions to OSA-induced atherosclerosis. ResultsAtherosclerotic lesions were compared between conventionally-reared specific pathogen free (SPF) and germ-free (GF) ApoE-/- mice following a high fat high cholesterol diet (HFHC), with and without IHC conditions. The fecal microbiota and metabolome were profiled using 16S rRNA gene amplicon sequencing and untargeted tandem mass spectrometry (LC-MS/MS) respectively. Phenotypic data showed that HFHC significantly increased atherosclerosis as compared to regular chow (RC) in both aorta and pulmonary artery (PA) of SPF mice. IHC exacerbated lesions in addition to HFHC. Differential abundance analysis of gut microbiota identified an enrichment of Akkermansiaceae and a depletion of Muribaculaceae (formerly S24-7) family members in the HFHC-IHC group. LC-MS/MS showed a dysregulation of bile acid profiles with taurocholic acid, taurodeoxycholic acid, and 12-ketodeoxycholic acid enriched in the HFHC-IHC group, long-chain N-acyl amides, and phosphatidylcholines. Interestingly, GF ApoE-/- mice markedly reduced atherosclerotic formation relative to SPF ApoE-/- mice in the aorta under HFHC/IHC conditions. In contrast, microbial colonization did not show a significant impact on the atherosclerotic progression in PA. ConclusionsIn summary, this research demonstrated that (1) IHC acts cooperatively with HFHC to induce atherosclerosis; (2) gut microbiota modulate atherogenesis, induced by HFHC/IHC, in the aorta not in PA; (3) different analytical methods suggest that a specific imbalance between Akkermansiaceae and Muribaculaceae bacterial families mediate OSA-induced atherosclerosis; and (4) derived bile acids, such as deoxycholic acid and lithocholic acid, regulate atherosclerosis in OSA. The knowledge obtained provides novel insights into the potential therapeutic approaches to prevent and treat OSA-induced atherosclerosis.

microbiology↗

bioRxiv2024

Productivity of the eelgrass biotope and the resilience of fisher-hunter-gatherers in prehistoric Denmark

In the shallow coastal waters of the Danish archipelago, eelgrass (Zostera marina) forms extensive and extremely productive stands, which support food webs that are isotopically distinct from those based on the primary productivity of marine phytoplankton. The isotopic signatures of eelgrass and phytoplankton food webs explain much of the variation in {delta}13C, {delta}15N and {delta}34S values in marine vertebrate remains recovered from prehistoric coastal sites in Denmark. Isotope data from human and dog remains reflect the overwhelming importance of the eelgrass biotope to the fisher-hunter-gatherer (FHG) subsistence during the Late Mesolithic Ertebolle epoch ([~]7400-5800 cal BP). By recognising eelgrass and pelagic resources as isotopically distinct, we obtain more accurate diet reconstructions and dietary 14C reservoir effect corrections for Ertebolle individuals. Longstanding research issues, including technology, palaeodemography, and the resilience and sustainability of the FHG economy need to be reassessed in view of the isotopic signature and productivity of the eelgrass biotope in Danish waters. Eelgrass productivity is also pertinent to comparisons between Ertebolle and Neolithic economies in Denmark, and between FHG adaptations in Denmark and neighbouring regions, and may be key to understanding the much-discussed delay in the transition to farming.

ecology↗

bioRxiv2023

Dietary 14C reservoir effects and the chronology of prehistoric burials at Sakhtysh, central European Russia

We present the first robust radiocarbon (14C) chronology for prehistoric burial activity at Sakhtysh, in European Russia, where nearly 180 inhumations attributed to Lyalovo and Volosovo pottery-using hunter-gatherer-fishers represent the largest known mortuary populations of these groups. Past attempts at 14C dating were restricted by poor preservation and limited understanding of diet and dietary 14C reservoir effects (DREs). We obtained 32 new AMS (Accelerator Mass Spectrometry) 14C dates on human petrous bones. Dietary stable isotopes ({delta}13C, {delta}15N) for all AMS-dated human samples allow us to propose a novel DRE correction model, using differences in 14C, {delta}13C and {delta}15N from bones and teeth of the same individuals to predict DREs of up to c.900 14C years. Our chronological model for 40 individuals dates Lyalovo burials to the early 5th millennium cal BC, and Volosovo burials to the mid-4th to early 3rd millennium. It reveals a previously unrecognised shift in the Volosovo subsistence economy at c.3300 cal BC, coinciding with a reorientation of trade networks, and shows that the last burial at Sakhtysh was the only one in a crouched position, which coincided with the beginning of Fatyanovo practices, the regional expression of the Yamnaya/Corded Ware expansion.

ecology↗

bioRxiv2019

Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe

The Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.

evolutionary biology↗