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Department of Veterinary Medicine

Cambridge Veterinary School
 

Modelling Human Gut-Microbiome Interactions in a 3D Bioelectronic Platform

Fri, 11/04/2025 - 11:00

Small Sci. 2024 Apr 22;4(6):2300349. doi: 10.1002/smsc.202300349. eCollection 2024 Jun.

ABSTRACT

The role of the gut microbiome in various aspects of health and disease is now a well-established concept in modern biomedicine. Numerous studies have revealed links between host health and microbial activity, spanning from digestion and metabolism to autoimmune disorders, stress and neuroinflammation. However, the exact mechanisms underlying this complex cross-talk still remain a mystery. Conventionally, studies examining host-microbiome interactions rely on animal models, but translation of such findings into human systems is challenging. Bioengineered models represent a highly promisingapproach for tackling such challenges. Here, a bioelectronic platform, the e-transmembrane, is used to establish a 3D model of human intestine, to study the effects of microbiota on gut barrier integrity. More specifically, how postbiotics and live bacteria impact the morphology and function of the intestinal barrier is evaluated. e-Transmembrane devices provide a means for in-line and label-free continuous monitoring of host-microbe cross-talk using electrochemical impedance spectroscopy, revealing distinct patterns that emerge over 24 hours. Microscopy and quantification of molecular biomarkers further validate the differential effects of each bacterial intervention on the host tissue. In addition, a framework to better study and screen drug candidates and potential therapeutic/dietary interventions, such as postbiotics and probiotics, in more physiologically relevant human models is provided.

PMID:40212761 | PMC:PMC11935216 | DOI:10.1002/smsc.202300349

Common variants in the CPT1A gene are associated with cataracts in Northern breeds of domestic dog

Fri, 04/04/2025 - 11:00

PLoS One. 2025 Apr 4;20(4):e0320878. doi: 10.1371/journal.pone.0320878. eCollection 2025.

ABSTRACT

Primary hereditary cataract affects many purebred domestic dog breeds and is a major cause of visual impairment in dogs. Cataracts are common in Northern breeds such as the Siberian Husky, Alaskan Malamute and Samoyed, but their aetiology is currently unknown. Only two genetic loci are known to be causally related to primary hereditary cataracts in the dog. To search for genetic loci associated with cataracts in Northern breeds, we used a genome-wide association study approach in three breeds-Siberian Husky, Alaskan Malamute and Samoyed. Cases were defined as dogs with bilateral posterior polar subcapsular cataracts and controls were at least four years of age with no evidence of cataracts or other ocular abnormality. We found a genome-wide statistical association for cataracts in the Siberian Husky on canine chromosome 18 (P-value: 1.1 x 10 - 7), which was independently replicated in a second larger case-control set (P-value 9.8 x 10 - 29). The Samoyed breed also showed evidence for association in the same genomic region (P-value: 2.4 x 10 - 5). We subsequently used targeted resequencing of the associated region (6.5 Mb) in ten Siberian Huskies and whole genome sequencing of a Husky, Malamute, Samoyed and Norwegian Buhund case to conduct fine-mapping and screen for candidate causal variants. These analyses identified a region of linkage disequilibrium in the four breeds containing common variants in the carnitine palmitoyltransferase 1A (CPT1A) gene that are strongly associated with bilateral posterior polar subcapsular cataracts in the Siberian Husky, Samoyed, Icelandic Sheepdog and Norwegian Buhund and we demonstrate that CPT1A is expressed in the dog lens and retina through RNAseq. Our findings represent a novel locus for cataracts in dogs. However, further work is needed to elucidate the pathophysiology underlying the association between CPT1A and cataracts in Northern breeds.

PMID:40184359 | DOI:10.1371/journal.pone.0320878

Early calf segregation enables development of bovine tuberculosis-free replacement stock in a highly infected dairy herd: a preliminary study in Ethiopia

Thu, 03/04/2025 - 11:00

Front Vet Sci. 2025 Mar 19;12:1551065. doi: 10.3389/fvets.2025.1551065. eCollection 2025.

ABSTRACT

Bovine tuberculosis (bTB) severely impacts Ethiopia's growing dairy sector, where test-and-cull control methods are economically unfeasible, and test-and-segregation is impractical in herds with very high prevalence. We assessed the feasibility of establishing bTB-free replacement stock through early segregation of calves born to bTB-positive cows. In a two-year longitudinal study on a high-prevalence (98% tuberculin skin test positive) dairy farm, 26 newborn calves were separated from their bTB-positive dams on day five after birth and screened for bTB at 2 to 5 month intervals across eight rounds, with test-positive calves immediately removed from the negative herd. The majority of segregated calves (19 out of 25; 76%; 95% CI: 58-94) remained bTB-test negative through the testing period, with nine uninfected female calves and two males reaching 18 months of age, demonstrating potential for establishing bTB-free breeding stock. However, six calves (24%; 95% CI: 6-42) turned to test positive during the study period. The extended dam-calf contact during the first five days likely contributed to some infections, suggesting that immediate separation and alternative colostrum sources could improve success rates. The addition of interferon gamma release assays in later testing rounds enabled detection of infected animals potentially missed by skin testing alone, highlighting the value of complementary diagnostic approaches for surveillance. These findings provide preliminary evidence that early calf segregation can generate bTB-negative replacement stock from infected herds, and provide a framework for larger-scale studies across different farm settings.

PMID:40177672 | PMC:PMC11963379 | DOI:10.3389/fvets.2025.1551065

Embracing the unknown: Proteomic insights into the human microbiome

Wed, 02/04/2025 - 11:00

Cell Metab. 2025 Apr 1;37(4):799-801. doi: 10.1016/j.cmet.2025.02.003.

ABSTRACT

Protein-level investigations into the human microbiome provide insights into active microbial functions. Recently, Valdés-Mas et al.1 introduced a metagenome-informed metaproteomics approach to functionally explore species-level microbiome-host interactions and quantify the dietary exposome. Its potential has been implemented in mice and humans to uncover proteomic signatures of health and inflammatory bowel disease.

PMID:40174574 | DOI:10.1016/j.cmet.2025.02.003