Biology subjects

Limborg, M. T.

Publications and source records attributed to Limborg, M. T..

7 recordsLinked to original sources

bioRxiv2025

Dietary fibre promotes chronic whipworm infection through direct and time-dependent modulation of innate immunity

Dietary fibre regulates the microbiome and gut health but increases murine whipworm (Trichuris muris) infection through unclear mechanisms. We show that mice fed inulin-supplemented diets exhibit dysregulated innate antimicrobial defences and altered tryptophan metabolism during T. muris infection. Inhibiting tryptophan catabolism or neutralizing IL-27 and IL-18 in inulin-fed mice restored infection resistance. Notably, inulin led to chronic infection even in microbiota-depleted mice. Removing inulin within a critical immune development window rapidly restored anti-helminth immunity, indicating direct, time-dependent modulation of mucosal immune responses. Our findings reveal a previously unrecognized, direct influence of dietary fibre on mucosal immunity to parasitic infection, independent of the microbiome, highlighting the complex interplay between diet timing and host defence.

microbiology↗

bioRxiv2025

Sample-specific CpG loci are important for accurate long-read methylation analysis

Methylated CpG loci mutate at high rates, but it remains challenging to identify sample-specific non-reference CpG loci for methylation analyses. Here, we present a likelihood-based method that identifies sample-specific CpG loci at high precision in long-read sequencing data from Nanopore and PacBio platforms. Inclusion of non-reference CpG loci increased the number of loci and reduced reference bias, and is important for accurate estimation of global methylation levels across samples.

genomics↗

bioRxiv2025

Amoebic gill disease (AGD) in Atlantic Salmon investigated through a holo-omic lens

Interactions between host genetics and the resident microbiota are complex. Understanding these interactions offers interesting alternatives for addressing gill health and disease resistance in salmonids. Amoebic gill disease (AGD), caused by Neoparamoeba perurans, remains a threat to Atlantic salmon, particularly in aquaculture settings where prevention and treatment options are scant. Selective breeding or genetic engineering towards increased AGD resilience present viable prevention strategies. While a number of studies have addressed AGD resistance in Atlantic salmon using transcriptomic and quantitative genetic approaches, the role of the Atlantic salmon gill microbiota in influencing AGD resilience and susceptibility needs further investigation. Addressing this, we leveraged a holo-omic approach using 16S rRNA bacterial profiling, and quantitative genetics, by considering the microbiota as an extended resistance trait of the salmon. We investigated the microbiota of AGD challenged Atlantic salmon in terms of two common resistance indicator traits: gill score and amoebic load. Subsequently we performed a GWAS using both the traditional indicator traits and traits of the microbiota. We found that the gill microbiota of the AGD affected salmon in this study was dominated by two bacterial families Simkaniaceae and Arcobacteracea. We found that microbial diversity and the relative abundance of Simkaniaceae, potentially derived from the amoeba, varied moderately with indicator traits. Additionally we identified several genomic regions that showed suggestive association with gill score and traits of the microbiota, and explored potential candidate genes for AGD resistance. Although much is still unclear regarding gill microbiota dynamics in gill disease, this study highlights the potential of addressing AGD through an integrative approach that considers the interplay between host genetics, the microbiota, and their roles in disease resistance.

genomics↗

bioRxiv2024

The need for high-resolution gut microbiome characterization to design efficient strategies for sustainable aquaculture production

Microbiome-directed dietary interventions such as microbiota-directed fibers (MDFs) have a proven track record in eliciting responses in beneficial gut microbes and are increasingly being promoted as an effective strategy to improve animal production systems. Here we used initial metataxonomic data on fish gut microbiomes as well as a wealth of a priori mammalian microbiome knowledge on -MOS and {beta}-mannan-derived MDFs to study effects of such feed supplements in Atlantic salmon (Salmo salar) and their hitherto poorly characterized gut microbiomes. Our multi-omic analysis revealed that the investigated MDFs (two -mannans and an acetylated {beta}-galactoglucomannan), at a dose of 0.2%, had negligible effects on both host gene expression, and gut microbiome structure and function under studied conditions. While a subsequent trial using a higher (4%) dietary inclusion of {beta}-mannan significantly shifted the gut microbiome composition, there were still no biologically relevant effects on salmon metabolism and physiology. Only a single Burkholderia-Caballeronia-Paraburkholderia (BCP) population demonstrated consistent and significant abundance shifts across both feeding trials, although with no evidence of {beta}-mannan utilization capabilities or changes in gene transcripts for producing metabolites beneficial to the host. In light of these findings, we revisited our omics data to predict and outline novel and potentially beneficial endogenous lactic acid bacteria that should be targeted with future, conceivably more suitable, MDF strategies for salmon. IMPORTANCEThis study focuses on the potential of MDFs to improve aquaculture production. Despite preliminary 16S rRNA amplicon data suggested that populations in the salmon gut microbiome could utilize structurally complex mannans, our findings indicates that endogenous microbes could not metabolize it, nor the host responds to its dietary inclusion, at least not under the trial conditions investigated in this study. We highlight that high-resolution and host-specific microbiome characterization can greatly improve trial design and selection of candidate MDFs for future nutritional interventions. Understanding the intricate interplay between host and its gut microbiome is paramount in studies seeking to leverage endogenous microbial communities to benefit the host. While each new condition, whether it is a disease onset or a nutritional stressor, has the potential to profoundly reshape the microbial diversity, composition and outputs, the functional microbiome information gained under healthy conditions represent a pivotal step towards designing more effective trials involving microbiome-reprogramming feed additives. Overall, we envisage that these results will lead to improved focus on coupling fundamental microbiome characterization to the design of next-generation feeds for salmon aquaculture.

microbiology↗

bioRxiv2023

SAMPLING THE ZEBRAFISH GUT MICROBIOTA - A GENOME RESOLVED METAGENOMIC APPROACH

The zebrafish is a promising model organism in the field of functional microbiota research. However, studies on the functional landscape of the zebrafish gut microbiota through shotgun based metagenomics are scarce. Thus, there is a lack of consensus regarding an appropriate sampling method that accurately represents the zebrafish gut microbiota. To address this, we sought to systematically test and evaluate four different methods of sampling the zebrafish gut microbiota: collection of feces from the tank, the whole gut, intestinal content and the application of ventral pressure to facilitate extrusion of gut material. In addition, we included water samples as an environmental control to address the potential influence of the environmental microbiota on the data interpretation. To compare these sampling methods in a context of microbiota-based studies we employed a combination of genome resolved metagenomics and 16S metabarcoding techniques. We observed differences among sample types on all levels including sampling, bioinformatic processing, metagenome co-assemblies, generation of metagenome-assembled genomes (MAGs), functional potential, MAG coverage and micro-diversity. Furthermore, our comparison to the environmental control demonstrated the potential impact of the environmental contamination on data interpretation. The findings emphasise the importance of considering the choice of sampling method. While all sample types tested are informative about the zebrafish gut microbiota, the optimal sample type depends on the specific objectives of the study.

microbiology↗

bioRxiv2023

The Salmon Microbial Genome Atlas enables novel insights into bacteria-host interactions via functional mapping

The essential role of the gut microbiota for host health and nutrition is well established for many terrestrial animals, while its importance for fish and particularly Atlantic salmon is unclear. Here, we present the Salmon Microbial Genome Atlas (SMGA) originating from wild and farmed fish both in freshwater and seawater, and consisting of 211 high-quality bacterial genomes, recovered by cultivation (n=131) and gut metagenomics (n=80). Bacterial genomes were taxonomically assigned into 14 different orders, including 28 distinctive genera and 31 potentially novel species. Benchmarking the SMGA, we functionally characterized key populations in the salmon gut that were detected in vivo. This included the ability to degrade diet-derived fibers and release vitamins and other exo-metabolites with known beneficial effects, which were validated by in vitro cultivation and untargeted metabolomics. Together, the SMGA enables high resolution functional insight into salmon gut microbiota with relevance for salmon nutrition and health.

microbiology↗

bioRxiv2023

Host-gut microbiota interactions shape parasite infections in farmed Atlantic salmon

Animals and their associated microbiota share long evolutionary histories. Both host genotype and associated microbiota influence phenotypes such as growth and disease resilience. We applied a hologenomic approach to explore the relationship between host and microbiota in shaping lifetime growth and parasitic cestode infection in farmed Atlantic salmon. Genomes, transcriptomes, metabolomes and metagenomes were generated from the guts of 460 harvest-aged salmon, 82% of which were naturally infected with an intestinal cestode. One salmonid-specific Mycoplasma dominated the gut microbiota of uninfected salmon. However, the microbiota was perturbed in smaller, parasitised fish, with increased abundance of Vibrionaceae and other Mycoplasma species previously linked to the cestode microbiota. The cestode-associated Mycoplasma carry more virulence-associated genes than the salmonid Mycoplasma. Colonisation by one cestode-associated Mycoplasma was associated with a region of the salmon genome encoding several long noncoding RNA genes previously associated with host control of intestinal microbiota. Integrating the multiple omic datasets revealed coordinated changes in the salmon gut transcriptome and metabolome that correlated with shifts in the microbiota of smaller, parasitised fish. Our results suggest that cestode infections introduce new microbes and trigger host responses, altering the gut microbiota with increases in potentially pathogenic microbes. Establishment of these microbes is partially shaped by the genetic background of the host. Our study highlights the value of a hologenomic approach for gaining an in-depth understanding of trilateral interactions among host, microbiota and parasite.

systems biology↗