Biology subjects

Russell, J.

Publications and source records attributed to Russell, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Pan-genomic and pan-transcriptomic analysis of the Heavy Metal ATPase family reveals diverse expression patterns and functional roles in barley

Heavy metals act as essential metalloprotein cofactors in numerous physiological processes but can become toxic when non-essential metals accumulate or when essential metals are in excess. As plants continuously encounter heavy metals through their roots, they have evolved complex homeostatic mechanisms to regulate metal uptake and distribution. The Heavy Metal ATPase (HMA) gene family encodes a group of heavy metal transporting P-type ATPases that have been linked to stress resistance and nutrient supply. Here, we used a bioinformatics approach to identify and characterise 13 HMA genes containing characteristic P1B-type ATPase domains and motifs in the barley Morex V3 reference genome. The genes are located on five of the seven barley chromosomes. Phylogenetic analysis revealed that they cluster into five sub-clades, including one clade unique to barley. Expression profiling across multiple datasets showed distinct temporal and tissue-specific expression patterns among HvHMAs, with several members exhibiting significant transcriptional responses to specific biotic and abiotic stresses. By utilising recently available pan-transcriptomic and pan-genomic resources, we have identified substantial allelic diversity and inter-accession variation in HvHMAs. Our findings suggest that HvHMAs have functions extending beyond canonical heavy metal homeostasis and warrant further investigation for their potential roles in broader physiological and stress-related processes.

plant biology↗

bioRxiv2026

Chromosome-Specific Expansion and Diversification of the Thionin Gene Family in Barley

Thionins are cysteine-rich peptides involved in plant defense. However, their genomic organization, evolutionary expansion, and potential function in barley remain unclear. Here, we integrated reference genome, pan-genome, and pan-transcriptome resources to systematically characterize the thionin gene family in barley. Fifty-six thionin genes were identified in the reference genome Morex V3, displaying pronounced chromosomal clustering and high sequence conservation consistent with extensive tandem duplication. Promoter analysis of these genes revealed enrichment of cis-acting elements associated with stress- and hormone-related signaling pathways, suggesting a potential role for thionins in biotic stress responses, including aphid defense, as suggested by previous studies. Analysis of 20 barley genotypes revealed substantial copy number variation, particularly on chromosomes 6H and 7H, indicating dynamic population-level expansion. Sequence-based clustering grouped thionins into ten clusters and five singletons, with major clusters corresponding to specific chromosomes. Integration of pan-transcriptome data showed that transcriptional activity was largely confined to four major clusters. Aphid infestation of four genotypes featuring copy number variation in chr 6H thionin genes resulted in a strong induction of thionin gene expression, with more pronounced responses during poor-host interactions. Aphid-induced expression tended to increase with thionin gene number, however, this no correlation was observed regarding basal gene expression levels. Together, these findings indicate that the thionin gene family in barley has undergone species-specific expansion driven by tandem duplication and contributes to genotype-dependent aphid defense responses.

Plant Biology↗

bioRxiv2026

PPa1 insufficiency drives lysosomal storage disease and inflammatory macrophage expansion in the bone marrow.

Inorganic pyrophosphatase-1 (PPa1) is an essential enzyme proposed to limit accumulation of the ubiquitous metabolic byproduct inorganic pyrophosphate, yet its role beyond a general housekeeping function remains poorly understood. We generated viable hypomorphic alleles of PPa1 through random mutagenesis in mice and unexpectedly found that PPa1 insufficiency causes a lysosomal storage disease of the bone marrow. Mutant mice developed impaired hematopoiesis and defective skeletal mineralization in a hematopoietic-intrinsic manner. The bone marrow was infiltrated by glycolipid-laden macrophages that were marked by high Spp1 and CD14 expression, blunted lysosomal acidification, metabolic stress, and a distinct inflammatory transcriptional program. Consistent with a lysosomal storage defect, PPa1-deficient bone marrow accumulated elevated levels of long-chain glucosyl-sphingolipids and sphingosine. These findings identify PPa1 as a previously unrecognized regulator of lysosomal function in myeloid cells that restrains inflammatory macrophage expansion and prevents bone marrow lysosomal storage pathology.

immunology↗

bioRxiv2025

Post-Domestication selection of MKK3 Shaped Seed Dormancy and End-Use Traits in Barley

Anthropogenic selection of grain traits such as dormancy has shaped the developmental trajectories of crop plants (1). In cereals, shortening dormancy provides rapid and even post-harvest germination, but increases the risk of weather-induced pre-harvest sprouting (PHS) with harvest losses estimated at beyond 1 billion USD a year (2, 3, 4). Our understanding of how, why, when and where diversification of cereal dormancy arose is fragmentary. Here, we show in the founder cereal crop barley (Hordeum vulgare) that the Mitogen-Activated Protein Kinase (MAPK) pathway regulates dormancy primarily through a mosaic of locus haplotypes comprising copy-number variation and inherent kinase activity of Mitogen-activated protein kinase kinase 3 (MKK3). We provide evidence supporting the historical selection of specific MKK3 haplotypes that shape dormancy levels according to changing climatic pressures. Understanding the regulatory landscape of MKK3 provides a genetic framework to balance short grain dormancy and PHS-avoidance during a period of rapid climate change.

plant biology↗

bioRxiv2024

New loci and candidate genes in spring two-rowed barley detected through meta-analysis of a field trial European network

This study contributes new knowledge on quantitative trait loci (QTLs) and candidate genes for adaptive traits and yield in two-rowed spring barley. A meta-analysis of a network of field trials, varying in latitude and sowing date, with 151 cultivars across several European countries, increased QTL detection power compared to single-trial analyses. The traits analysed were heading date (HD), plant height (PH), thousand-grain weight (TGW), and grain yield (GY). Breaking down the analysis by the main genotype-by-environment trends revealed QTLs and candidate genes specific to conditions like sowing date and latitude. A historical look on the evolution of QTL frequencies revealed that early selection focused on PH and TGW, likely due to their high heritability. GY selection occurred later, facilitated by reduced variance in other traits. The study observed that favourable alleles for plant height were often fixed before those for grain yield and TGW. Some regions showed linkage in repulsion, suggesting targets for future breeding. Several candidate genes were identified, including known genes and new candidates based on orthology with rice. Remarkably, the deficiens allele of gene Vrs1, appears associated to higher GY. These findings provide valuable insights for barley breeders aiming to improve yield, and other agronomic traits. HighlightA dense genome-wide meta-analysis provides new QTLs, reveals breeding history trends and identifies new candidate genes for yield, plant height, grain weight and heading time of spring barley.

genetics↗

bioRxiv2024

Characterization of Multicellular Niches Supporting Hematopoietic Stem Cells Within Distinct Zones

Previous studies of hematopoietic stem cells (HSCs) primarily focused on single cell-based niche models, yielding fruitful but conflicting findings1-5. Here we report our investigation on the fetal liver (FL) as the primary fetal hematopoietic site using spatial transcriptomics. Our study reveals two distinct niches: the portal-vessel (PV) niche and the sinusoidal niche. The PV niche, composing N-cadherin (N-cad)HiPdgfr+ mesenchymal stromal cells (MSCs), endothelial cells (ECs), and N-cadLoAlbumin+ hepatoblasts, maintains quiescent and multipotential FL-HSCs. Conversely, the sinusoidal niche, comprising ECs, hepatoblasts and hepatocytes, as well as potential macrophages and megakaryocytes, supports proliferative FL-HSCs biased towards myeloid lineages. Unlike prior reports on the role of Cxcl12, with its depletion from vessel-associated stromal cells leading to 80% of HSCs reduction in the adult bone marrow (BM)6,7, depletion of Cxcl12 via Cdh2CreERT (encoding N-cad) induces altered localization of HSCs from the PV to the sinusoidal niches, resulting in an increase of HSC number but with myeloid-bias. Similarly, we discovered that adult BM encompasses two niches within different zones, each composed of multi-cellular components: trabecular bone area (TBA, or metaphysis) supporting deep-quiescent HSCs, and central marrow (CM, or diaphysis) fostering heterogenous proliferative HSCs. This study transforms our understanding of niches by shifting from single cell-based to multicellular components within distinct zones, illuminating the intricate regulation of HSCs tailored to their different cycling states.

developmental biology↗

bioRxiv2024

Opportunities to improve the recommendation of plant varieties under the Recommended List (RL) system

Recommended List (RL) is the UK plant variety recommendation system introduced in 1944 for supporting growers in making decisions on variety choices. The current analysis for RL is largely based on published works on trial designs and statistical analyses in the 1980s. Given the statistical advances that have been developed and adopted elsewhere, it is timely to review and update the methods for data analysis in RL. In addition, threats from climate change challenge the prediction of variety performance in future environments. Better variety recommendations, particularly for matching varieties to specific environments can be achieved through improved modeling of effects from genetics, environments and genetic by environment interactions. Here, we evaluated grain yield data from 153 spring barley varieties that were trialed for RL from 2002 to 2019. Our results show that the available methods for predicting variety performance are poor and inconsistent across environments without any clearly superior method. However, these shortcomings can be easily overcome by switching the statistical model for analyzing RL data to one that fits variety effects as random and accounts for genetic relationships among varieties. Lastly, we also discuss other possible approaches for analyzing RL data and highlight the relevance of genomics in both variety registration and recommendation.

genetics↗

bioRxiv2024

A major effect locus involved in migration timing is shared by pink and sockeye salmon

AbstractWhole genome duplication (WGD) provides evolutionary opportunities to increase biological complexity and phenotypic diversity by selective retention of duplicated genes. We identify a small genomic region in salmon that governs complex life history variation and has diversified across four WGDs to fine-tune trait expression. Within this region, three large-effect loci on three chromosomes modulate migration timing across four species - a critical trait optimizing fitness by synchronizing reproduction and environmental conditions. Life history and genome resequencing data support intraspecific evolution of polymorphisms related to early- and late-reproducing phenotypes. We demonstrate that the repeated evolution of loci underlying reproductive timing carries the signature of WGD-facilitated adaptive evolution. This adaptation is driven by the subsequent subfunctionalization of genes within the highly conserved HPG axis, which regulates vertebrate reproduction.

genomics↗

bioRxiv2024

Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration.

Injury is a common occurrence in the life of organisms. Because the extent of damage cannot be predicted, injured organisms must determine how much tissue needs to be restored. It is known that amputation position determines the regeneration speed of amputated appendages in regeneration-competent animals. Yet, it is not clear how positional information is conveyed during regeneration. Here, we investigated tissue dynamics in regenerating caudal fins in the African killifish (Nothobranchius furzeri). We report position-specific, differential modulation of the spatial distribution, duration, and magnitude of proliferation. Regenerating fins profiled by single cell RNA sequencing identified a Transient Regeneration-Activated Cell State (TRACS) that is amplified to match a given amputation position. We located this TRACS to the basal epidermis and found them to express components and modifiers of the extracellular matrix (ECM). We propose a role for these cells in transducing positional information to the regenerating blastema by remodeling the ECM. HighlightsO_LIAmputation position changes tissue-wide proliferation response C_LIO_LITranscriptional compartmentalization is relative to injury type C_LIO_LIRegeneration deploys Transient Regeneration-Activated Cell States C_LIO_LIPrediction: positional information is transduced by ECM changes during regeneration C_LI

developmental biology↗

bioRxiv2023

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T cell function. Through forward genetic screening in mice, we discovered that loss-of-function mutations in LDL receptor related protein 10 (Lrp10) caused naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. Lrp10 was induced with T cell activation and its expression post-translationally suppressed IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhanced T cell homeostatic expansion through IL7R signaling. Lrp10-deficient mice were also intrinsically resistant to syngeneic tumors. This phenotype depended on dense tumor infiltration of CD8 T cells that displayed increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.

immunology↗

bioRxiv2023

Sugar assimilation underlying dietary evolution of Neotropical bats

Specializations in animal diets drive selective demands on morphology, anatomy, and physiology. Studying adaptations linked to diet evolution benefits from examining Neotropical bats, a remarkable group with high taxonomic and trophic diversity. In this study, we performed glucose tolerance tests on wild-caught bats, which revealed distinct responses to three sugars present in different foods: trehalose (insects), sucrose, and glucose (fruits and nectar). Insect-eating bats metabolism responded most strongly to trehalose, while bats with nectar and fruit-based diets exhibited a heightened response to glucose and sucrose, reaching blood glucose levels over 600 and 750 mg/dL. To search for signatures of positive selection in sugar assimilation genes we performed genome analysis of 22 focal bat species and 2 outgroup species. We identified selection in the ancestral vespertilionid branch (insect-eaters) for the digestive enzyme trehalase, while sucrase-isomaltase exhibited selection in branches leading to omnivorous and nectar diets. Unexpectedly, the insect-eating lineage Myotis exhibited sucrase-isomaltase selection, potentially explaining their heightened sucrose assimilation. Furthermore, the genes encoding for glucose transporters, Slc2a3 and Slc2a2, showed selection in nectar and blood feeding bats, with analyses of predicted protein structures supporting modified activity. By examining cellular features of the small intestine, we discovered that dietary sugar proportion strongly impacted numerous digestive traits, providing valuable insight into the physiological implications of the identified molecular adaptations. To elucidate this further, we used HCR RNA-FISH to perform single molecule ex vivo gene expression analysis of enterocyte response to a glucose meal in three focal species. We observed unusually high activity in the glucose transporter Slc2a2 during the fasted state of nectar bats that did not change upon feeding. Comparatively, nectar bats exhibited an enhanced capacity for intestinal absorption of dietary sugar primarily through Slc2a2, while fruit bats relied on increasing levels of Slc5a1. Overall, this study highlights the intricate interplay between molecular, morphological, and physiological aspects of diet evolution and provides new insights into our understanding of dietary diversification and sugar assimilation mechanisms in mammals. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/547432v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@744e5dorg.highwire.dtl.DTLVardef@1c4e6fcorg.highwire.dtl.DTLVardef@18baaforg.highwire.dtl.DTLVardef@18853ee_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISugar assimilation differences emphasize metabolic adaptations to diet C_LIO_LIGlucose tolerance tests provide a quick and practical assessment of dietary ecology C_LIO_LIBat genomes exhibit positive selection on digestive enzymes and glucose transporters C_LIO_LIStructural comparisons of proteins suggest altered activity of glucose transporters C_LIO_LIGlucose absorption differences can be explained by gut anatomy C_LIO_LIIntestinal villus diversity and novel microanatomy in bats C_LIO_LIExtreme blood glucose (above 600 and 750 mg/dL) coincides with constitutive expression of apical Slc2a2 C_LIO_LIThe regulation of apical Slc2a2 highlights differences in blood glucose levels C_LI

evolutionary biology↗

bioRxiv2023

Genomic resources for a historical collection of cultivated two-row European spring barley genotypes.

Barley genomic resources are increasing rapidly, with the publication of a barley pangenome as one of the latest developments. Two-row spring barley cultivars are intensely studied as they are the source of high-quality grain for malting and distilling. Here we provide data from a European two-row spring barley population containing 209 different genotypes registered for the UK market between 1830 to 2014. The dataset encompasses RNA-sequencing data from six different tissues across a range of barley developmental stages, phenotypic datasets from two consecutive years of field-grown trials in the United Kingdom, Germany and the USA; and whole genome shotgun sequencing from all cultivars, which was used to complement the RNA-sequencing data for variant calling. The outcomes are a filtered SNP marker file, a phenotypic database and a large gene expression dataset providing a comprehensive resource which allows for downstream analyses like genome wide association studies or expression associations.

plant biology↗

bioRxiv2023

Epidermal SIRT1 and BDNF modulate mechanical allodynia in mouse models of diabetic neuropathy

Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical pain. The role of skin mechanoreceptors in the development of mechanical pain (allodynia) is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating A{beta} axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia.

neuroscience↗

bioRxiv2022

Barley MLA3 recognizes the host-specificity determinant PWL2 from rice blast (M. oryzae)

Plant nucleotide-binding leucine-rich repeat immune receptors (NLRs) directly or indirectly recognize pathogen-secreted effector molecules to initiate plant defense. Recognition of multiple pathogens by a single NLR is rare and usually occurs via monitoring for changes to host proteins; few characterized NLRs have been shown to recognize multiple effectors. The barley NLR Mla has undergone functional diversification and Mla alleles recognize host-adapted isolates of barley powdery mildew (Blumeria graminis f. sp. hordei; Bgh). Here, we show that Mla3 also confers resistance to rice blast (Magnaporthe oryzae) in a dosage dependent manner. Using a forward genetic screen, we discovered that the recognized effector from M. oryzae is PWL2, a host range determinant factor that prevents M. oryzae from infecting weeping lovegrass (Eragrostis curvula). Mla3 has therefore convergently evolved the capacity to recognize effectors from diverse pathogens.

plant biology↗

bioRxiv2022

Converging pathways direct synapse elimination through the homeodomain transcriptional regulator DVE-1

An important step in brain development is the remodeling of juvenile neural circuits to establish mature connectivity. The elimination of juvenile synapses is a critical step in this process; however, the molecular mechanisms directing synapse elimination activities and their timing are not fully understood. We identify here a conserved transcriptional regulator, DVE-1, that shares homology with mammalian special AT-rich sequence-binding (SATB) family members and directs the elimination of juvenile synaptic inputs onto remodeling C. elegans GABAergic neurons. Dorsally localized juvenile acetylcholine receptor clusters and apposing presynaptic sites are eliminated during maturation of wild type GABAergic neurons but persist into adulthood in dve-1 mutants. The persistence of juvenile synapses in dve-1 mutants does not impede synaptic growth during GABAergic remodeling and therefore produces heightened motor connectivity and a turning bias during movement. DVE-1 is localized to GABAergic nuclei prior to and during remodeling and DVE-1 nuclear localization is required for synapse elimination to proceed, consistent with DVE-1s function as a transcriptional regulator. Pathway analysis of DVE-1 targets and proteasome inhibitor experiments implicate transcriptional control of the ubiquitin-proteasome system in synapse elimination. Together, our findings demonstrate a new role for a SATB family member in the control of synapse elimination during circuit remodeling through transcriptional regulation of ubiquitin-proteasome signaling. Contributions SummaryKDA generated strains, transgenic lines, molecular constructs, confocal microscopy images and analysis, performed optogenetic behavioral experiments, photoconversion experiments, modencode ChIP-seq analysis and pathway analysis. SR performed all calcium imaging experiments/analysis and conducted single worm tracking. KB performed all Bortezomib inhibitor experiments and analysis. CL generated most vectors and constructs. JR assisted with generation of CRISPR/Cas9 generated strains. WA and MR assisted with aldicarb behavioral assay. DO assisted with EMS screen and isolation of dve-1 mutant. CB and MD aided in CloudMap bioinformatic analysis of the uf171 mutant. MMF and KDA designed and interpreted results of all experiments and wrote the manuscript.

neuroscience↗

bioRxiv2022

M1 selective muscarinic allosteric modulation enhances cognitive flexibility and effective salience in nonhuman primates

Acetylcholine (ACh) in cortical neural circuits mediates how selective attention is sustained in the presence of distractors and how flexible cognition adjusts to changing task demands. The cognitive domains of attention and cognitive flexibility might be differentially supported by the M1 muscarinic cholinergic sub-receptor. Understanding how M1 mechanisms support these cognitive subdomains is of highest importance for advancing novel drug treatments for conditions with altered attention and reduced cognitive control including Alzheimers disease or schizophrenia. Here, we tested this question by assessing how the subtype selective M1-receptor specific positive allosteric modulator (M1 PAM VU0453595) affects visual search and flexible reward-learning in nonhuman primates. We found that allosteric potentiation of the M1 receptor enhanced flexible learning performance by improving extra-dimensional set shifting, by reducing latent inhibition of previously experienced distractors, and by reducing response perseveration in the absence of adverse side effects. These pro-cognitive effects occurred in the absence of apparent changes of attentional performance during visual search. In contrast, non-selective ACh modulation using the acetylcholinesterase inhibitor donepezil improved attention during visual search at doses that did not alter cognitive flexibility and that already triggered gastrointestinal cholinergic side effects. These findings illustrate that M1 positive allosteric modulation enhances cognitive flexibility without affecting attentional filtering of distraction, consistent with M1 activity boosting the effective salience of relevant over irrelevant objects. These results suggest that M1 PAMs are versatile compounds for enhancing cognitive flexibility in disorders spanning schizophrenia and Alzheimers diseases. Statement of significanceMuscarinic receptors mediate the pro-cognitive effects of acetylcholine, but it has remained unclear whether they differentially affect the cognitive subfunctions of attentional filtering, set shifting, and learning. To clarify the functional specificity of M1 receptors, we assessed these diverse functions using a recently developed, highly selective M1 PAM. This M1 PAM caused domain-specific cognitive improvement of flexible learning and extra-dimensional set shifting, reduced perseverations and enhanced target recognition during learning without altering attentional filtering functions. These domain-specific improvement contrasted to effects of a non-selective acetylcholinesterase inhibitor that primarily enhanced attention and caused dose limiting adverse side effects. These results demonstrate domain-specific improvements of cognitive flexibility suggesting M1 PAMs are versatile compounds for treating cognitive deficits in schizophrenia and Alzheimers disease.

neuroscience↗

bioRxiv2021

β-Catenin-NFκB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction

Expansion of biliary epithelial cells (BECs) during ductular reaction (DR) is observed in liver diseases including cystic fibrosis (CF), and associated with inflammation and fibrosis, albeit without complete understanding of underlying mechanism. Using two different genetic knockouts of {beta}-catenin, one with {beta}-catenin loss is hepatocytes and BECs (KO1), and another with loss in only hepatocytes (KO2), we demonstrate disparate long-term repair after an initial injury by 2-week choline-deficient ethionine- supplemented diet. KO2 show gradual liver repopulation with BEC-derived {beta}-catenin- positive hepatocytes, and resolution of injury. KO1 showed persistent loss of {beta}-catenin, NF-{kappa}B activation in BECs, progressive DR and fibrosis, reminiscent of CF histology. We identify interactions of {beta}-catenin, NF{kappa}B and CF transmembranous conductance regulator (CFTR) in BECs. Loss of CFTR or {beta}-catenin led to NF-{kappa}B activation, DR and inflammation. Thus, we report a novel {beta}-catenin-NF{kappa}B-CFTR interactome in BECs, and its disruption may contribute to hepatic pathology of CF.

pathology↗

bioRxiv2021

Deploying an in vitro gut model to assay the impact of a mannan-oligosaccharide prebiotic, Bio-Mos(R) on the Atlantic salmon (Salmo salar) gut microbiome.

Mannose-oligosaccharide (MOS) pre-biotics are widely deployed in animal agriculture as immunomodulators as well as to enhance growth and gut health. Their mode of action is thought to be mediated through their impact on host microbial communities and the associated metabolism. Bio-Mos is a commercially available pre-biotic currently used in the agri-feed industry. To assess Bio-Mos for potential use as a prebiotic growth promotor in salmonid aquaculture, we have modified an established Atlantic salmon in vitro gut model, SalmoSim, to evaluate its impact on the host microbial communities. Inoculated from biological triplicates of adult farmed salmon pyloric caeca compartments, the microbial communities were stabilised in SalmoSim followed by a twenty-day exposure to the prebiotic and in turn followed by an eight day wash out period. Dietary inclusion of MOS resulted in a significant increase in formate (p=0.001), propionate (p=0.037) and isovalerate (p=0.024) levels, correlated with increased abundances of several, principally, anaerobic microbial genera (Fusobacterium, Agarivorans, Pseudoalteromonas). DNA metabarcoding with the 16S rDNA marker confirmed a significant shift in microbial community composition in response to MOS supplementation with observed increase in lactic acid producing Carnobacterium. In conjunction with previous in vivo studies linking enhanced volatile fatty acid production alongside MOS supplementation to host growth and performance, our data suggests that Bio-Mos may be of value in salmonid production. Furthermore, our data highlights the potential role of in vitro gut models to augment in vivo trials of microbiome modulators. ImportanceIn this paper we report the results of the impact of prebiotic (MOS supplementation) on microbial communities within recently developed Atlantic salmon gut microbiome in vitro simulator. Our data suggest that Bio-Mos may be of value in salmonid production as it enhances volatile fatty acid production in the Atlantic salmon gut and correlates with a significant shift in microbial community composition with observed increase in lactic acid producing Carnobacterium. In conjunction with previous in vivo studies linking enhanced volatile fatty acid production alongside MOS supplementation to host growth and performance, our data suggest that Bio-Mos may be of value in salmonid production. Furthermore, our data highlights the potential role of in vitro gut models to augment in vivo trials of microbiome modulators.

bioengineering↗