Biology subjects

Newell, M.

Publications and source records attributed to Newell, M..

3 recordsLinked to original sources

bioRxiv2025

Age-related changes in the gut microbiota of a long-lived seabird suggest divergence from mammalian models

Gut microbiota plays key roles in shaping host development, immunity, and physiology. The assembly of vertebrate gut microbiota during early life follows relatively predictable trajectories across several mammalian species, largely driven by maternal transmission routes. However, birds lack these transmission mechanisms due to their oviparity, potentially leading to different age-related microbiota patterns. Here, we investigate gut microbiota variation in Atlantic puffin (Fratercula arctica) chicks and adults across six British populations using 16S rRNA amplicon sequencing. We find that chick microbiotas show strong population-level structuring that disappears in adults, with spatial patterns particularly pronounced in anaerobic bacteria. Puffin microbiotas become increasingly individualised and aerotolerant with age, while taxonomic richness remains stable - patterns that contrast with the convergent, richness-increasing trajectories observed in several mammalian species. Our results suggest that environmental exposure drives early-life microbiota assembly in birds, highlighting the value of avian systems for understanding vertebrate microbiota development beyond mammals.

ecology↗

bioRxiv2020

Docosahexaenoic acid significantly reduces tumor cell growth in preclinical models of ovarian cancer

Despite recent advances in diagnosis and treatment, ovarian cancer (OC) is the most lethal gynecological malignancy and improving the efficacy of chemotherapy is of great interest. This study increases our understanding of how dietary intervention with docosahexaenoic acid (DHA)-a supplement proven safe for human consumption - enhances the anti-cancer effects of conventional chemotherapy. Our results demonstrated synergistic cell killing by DHA and carboplatin in OC cell lines. Furthermore, DHA supplementation alone and in combination with carboplatin significantly reduced OC growth in a high-grade serous OC patient-derived xenograft mouse model. Carboplatin administered intraperitoneally significantly reduced tumor growth in DHA-fed mice compared to mice on the control diet. Intravenous carboplatin administration in combination with DHA reduced tumor growth similarly to carboplatin or DHA monotherapies. The DHA-induced reduction in tumor growth in this model was associated with increased tumor necrosis and improved survival. As such, our findings provide a strong rationale to move to clinical trials that will determine whether DHA supplementation enhances the efficacy and tolerance of cytotoxic chemotherapy in patients with OC.

cancer biology↗

bioRxiv2019

Type-2 diabetes with low LDL-C: genetic insights into a unique phenotype

Although hyperlipidemia is traditionally considered a risk factor for type-2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL-C increases T2D risk. We thus sought to comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that LDL-C was negatively associated with T2D (OR=0.43[0.41, 0.45] per mmol/L unit of LDL-C), despite positive associations of LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n=431,167) and the GLGC consortium (n=188,577), and T2D from the DIAGRAM consortium (n=898,130). We identified 31 loci associated with lower LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this phenotype, and 9 have previously been implicated in non-alcoholic fatty liver disease. Finally, two-sample Mendelian randomization analyses suggest that low LDL-C causes T2D, although causal interpretations are challenging due to pleiotropy. Our findings extend our current understanding of the higher T2D risk among individuals with low LDL-C, and of the underlying mechanisms, including those underlying the diabetogenic effect of LDL-C-lowering medications.

genetics↗