Biology subjects

Morgan, X. C.

Publications and source records attributed to Morgan, X. C..

11 recordsLinked to original sources

bioRxiv2026

Microbial-associated acylated putrescines as immunomodulatory molecules in inflammatory bowel diseases

The gut microbiota regulates intestinal immunity through metabolite production, yet most disease-associated metabolites remain functionally uncharacterized. In inflammatory bowel diseases (IBD), where the microbial metabolome is profoundly altered, we identify N-acyl putrescines as microbiome-associated metabolites enriched across two independent cohorts. N-oleoylputrescine (NOP) emerges as the primary immunomodulatory candidate, inducing robust transcriptional responses in dendritic cells and colonic organoids. Enterocloster species harboring nonribosomal peptide synthetase gene clusters synthesize NOP, confirmed by isotope-tracing in vitro and germ-free mouse colonization in vivo. NOP suppresses core IBD inflammatory pathways in mouse dendritic cells and human monocytes, reducing signatures of histologic inflammation and therapy non-response. NOP dampens inflammation in four colitis models, decreases myeloid cell NF-{kappa}B activation, and suppresses type 1 immune responses through a T cell-intrinsic mechanism. That NOP accumulates in IBD despite its anti-inflammatory properties reveals a holobiont defense strategy: the gut microbiota deploys immunomodulatory metabolites as a compensatory response to restore homeostasis.

immunology↗

bioRxiv2026

Enhanced multi-omic viral profiling from microbial community sequencing with BAQLaVa

Viruses are crucial components of microbial communities, both phage that infect bacterial community members as well as pathogenic and other eukaryotic viruses. However, they remain unobserved by most current technologies, due to combinations of experimental and analytical factors. To address the latter, we developed the BAQLaVa algorithm for high-resolution profiling of >120,000 viral species (viral genome bins, VGBs) via reference-based metagenome (MGX) or metatranscriptome (MTX) alignment to complementary nucleotide markers and proteome sets. In comprehensive benchmarking, BAQLaVa substantially outperformed alternatives, achieving species-level recall and precision regularly over 90%. We applied BAQLaVa to MGX and MTX samples from the HMP2 IBDMDB cohort to identify previously undescribed viral perturbations in inflammatory bowel diseases. Most notably, virome diversity was reduced in tandem with bacterial diversity during inflammation, in contrast to previous findings based on a narrower range of viral detection. A subset of viruses were enriched during IBD, associated with carriage of abortive infection anti-defense systems such as AbiL and PD-{lambda}-2, as well as genes involved in the regulation of lysogeny. Leveraging the corresponding viral profiles, we also inferred phage-host relationships using scalable co-occurrence and covariation signals, even in the absence of host references or genome annotations. By enabling high sensitivity and specificity viral profiling from metagenomes or metatranscriptomes, BAQLaVa provides a scalable framework for virome epidemiology and systematic analysis of virus-host interactions.

bioinformatics↗

bioRxiv2025

Commensal skin bacteria interact with the innate immunesystem to promote tail regeneration in Xenopus laevis tadpoles.

Xenopus laevis tadpoles regenerate their tails following partial amputation, however, for a brief developmental window, some undertake wound healing rather than regeneration. Inspired by links between microbiomes and human inflammatory disease, we asked how tadpole skin microbiomes and innate immunity influence the ability to regenerate tails. Having previously shown that lipopolysaccharide-Tlr4 signalling promotes regeneration, here, we demonstrate that the peptidoglycan-Tlr2 pathway is also involved. While tadpoles acquire their commensal skin bacteria from their mothers, analysis of mitochondrial haplotypes did not explain familial regenerative bias. Levels of endogenous lipopolysaccharides on tail tips were also not predictive of regenerative success, and shotgun sequencing indicated no difference in bacterial loads. To see if microbiome composition correlated with regenerative success, we sequenced 16S rRNA amplicons from 503 tadpole tail tips and mapped these to regenerative outcomes. While no one taxon appeared critical for regenerative success, higher proportions of Gram-positives correlated with successful regeneration. Our results suggest a previously undocumented role for Tlr2, peptidoglycan and Gram-positive commensal skin bacteria in tipping the balance from wound repair to regenerative programmes in Xenopus laevis refractory stage tadpoles.

developmental biology↗

bioRxiv2025

Item recognition is associated with gut microbiota composition in healthy humans

Murine studies show that the gut microbiota - the collection of the microbes residing in the large intestine - affects memory performance in the host. However, whether commensal gut bacteria are linked to human episodic memory remains unknown. Here, we investigated whether individual differences in episodic memory performance were associated with differences in the indigenous gut microbiota composition between individuals. We show that greater gut microbiota alpha diversity was associated with better item recognition and that gut microbiota dissimilarity index (beta diversity) between participants was associated with differences in their performance. Finally, our results suggest that Prevotella copri might play a role in the relationship between gut microbiota and human item recognition in healthy individuals. In a sample size larger than previous human studies and examining unmanipulated gut microbiota, we provide evidence that episodic memory in healthy humans is linked to their gut microbiota composition. SIGNIFICANCE STATEMENTUnderstanding the relationship between the gut microbiota - the collective of microbes in our gut - and human cognition represents a pivotal frontier in neuroscience. Our study dives into this quest by exploring the connection between the indigenous gut microbiota and episodic memory in healthy individuals. While prior research has illuminated this relationship in murine models, our study extends these findings to humans, providing compelling evidence that gut microbiota diversity and structural composition are associated with differences in episodic memory performance. By shifting the focus from probiotic-based interventions to the study of our commensal gut microbes, our findings shed light on how the gut microbiota, in its natural state, could be linked to interindividual differences in human cognition.

animal behavior and cognition↗

bioRxiv2023

The role of family and environment in determining the skin microbiome of captive aquatic frogs, Xenopus laevis

BackgroundThe amphibian skin microbiome has drawn interest due to the ecological threat posed by chytridiomycosis, which drives changes in symbiotic microbial communities and may be inhibited by certain bacterial taxa. However, skin microbes also play a role in amphibian tissue regeneration. Xenopus spp. are well-established model organisms used to study development, regeneration, genetics and disease. Husbandry protocols, including use of antibiotics and other sterilising agents, may affect experimental outcomes by altering microbiomes. It is therefore essential to improve our understanding of Xenopus microbiome characteristics and inheritance. We undertook bacterial 16S rRNA based sampling of a captive, closed Xenopus laevis colony. A total of 16 female frogs, their eggs, and tadpoles were sampled, covering multiple aquarium systems and tanks, along with testes from males used for in vitro fertilisation and a range of environmental samples. ResultsTank environments supported the most complex microbial communities. Mother frogs harboured the most diverse microbial communities of the frog life stages, with tadpole skin microbiomes being relatively simple. Frog samples were dominated by Proteobacteria and Bacteroidota. Rhizobium and Chryseobacterium were dominant in tadpoles, whereas mothers supported high proportions of Vogesella and Acinetobacter as well as Chryseobacterium. While the mothers habitats contained low levels of these taxa, the tadpoles environmental microbes were very similar to those on tadpole skin. A total of 34 genera were found to be differentially abundant between the mothers and tadpoles. Analysis of Bray-Curtis distances indicated that mother and tadpole microbiomes varied according to the mothers aquarium system, the tanks within them, and the individual mother. Source tracking analyses showed that egg jelly and tadpoles received a mean of approximately two thirds of their microbiomes via vertical transmission, although a sizeable proportion came from unknown sources at all life stages. ConclusionsThe skin of mother frogs appears to select for certain taxa that are otherwise present at low abundances in the environment. While tadpoles inherit a proportion of their microbiomes from their mothers via the egg, they support a distinct and less diverse microbial community than adult frogs. The microbiome varies between individual mothers, and is also affected by the aquarium system and individual tank within that the mother occupies.

microbiology↗

bioRxiv2021

Manipulating the microbiome alters regenerative outcomes in Xenopus laevis tadpoles vis lipopolysaccharide signalling

Xenopus laevis tadpoles can regenerate functional tails, containing spinal cord, notochord, muscle, fin, blood vessels and nerves, except for a brief refractory period at around one week of age. At this stage, amputation of the tadpoles tail may either result in scarless wound healing, or the activation of a regeneration programme, which replaces the lost tissues. We recently demonstrated a link between bacterial lipopolysaccharides and successful tail regeneration in refractory stage tadpoles, and proposed that this could result from lipopolysaccharides binding to Toll-like receptor 4 (TLR4). Here, we have used 16S rRNA sequencing to show that the tadpole skin microbiome is highly variable between sibships and that the community can be altered by raising embryos in the antibiotic gentamicin. Six gram-negative genera, including Delftia and Chryseobacterium, were over-represented in tadpoles that underwent tail regeneration. Lipopolysaccharides purified from a commensal Chryseobacterium spp. XDS4, an exogenous Delftia spp. or Escherichia coli could significantly increase the number of antibiotic-raised tadpoles that attempted regeneration. Conversely, the quality of regeneration was impaired in native-raised tadpoles exposed to the antagonistic lipopolysaccharide of Rhodobacter sphaeroides. Editing TLR4 using CRISPR/Cas9 also reduced regeneration quality, but not quantity, at the level of the cohort. However, we found that the editing level of individual tadpoles was a poor predictor of regenerative outcome. In conclusion, our results suggest that variable regeneration in refractory stage tadpoles depends at least in part on the skin microbiome and lipopolysaccharide signalling, but that signalling via TLR4 cannot account for all of this effect.

developmental biology↗

bioRxiv2021

High-sensitivity pattern discovery in large, paired multi-omic datasets

Modern biological screens yield enormous numbers of measurements, and identifying and interpreting statistically significant associations among features is essential. Here, we present a novel hierarchical framework, HAllA (Hierarchical All-against-All association testing), for structured association discovery between paired high-dimensional datasets. HAllA efficiently integrates hierarchical hypothesis testing with false discovery rate correction to reveal significant linear and non-linear block-wise relationships among continuous and/or categorical data. We optimized and evaluated HAllA using heterogeneous synthetic datasets of known association structure, where HAllA outperformed all-against-all and other block testing approaches across a range of common similarity measures. We then applied HAllA to a series of real-world multi-omics datasets, revealing new associations between gene expression and host immune activity, the microbiome and host transcriptome, metabolomic profiling, and human health phenotypes. An open-source implementation of HAllA is freely available at http://huttenhower.sph.harvard.edu/halla along with documentation, demo datasets, and a user group. Author SummaryModern scientific datasets increasingly include multiple measurements of many complementary data types. Here, we present HAllA, a method and implementation that overcomes the statistical challenges presented by data of this type by using feature similarity within each dataset to find statistically significant groups of features between them. We applied HAllA to simulated and real datasets, showing that HAllA outperformed existing procedures and identified compelling biological relationships. HAllA is widely applicable to diverse data structures and presents the user with grouped results that are easier to interpret than traditional methods.

bioinformatics↗

bioRxiv2018

Role of Innate-like Lymphocytes in the Pathogenesis of Community Acquired Pneumonia

BackgroundMucosal-associated invariant T (MAIT) cells and V{delta}2+ {gamma}{delta} T cells are anti-bacterial innate-like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of bacterial infection. However, the role of ILLs in community-acquired pneumonia (CAP) is unknown.\n\nMethodsUsing sputum samples from a well-characterised CAP cohort, MAIT cell (V7.2-J12/20/33) and V{delta}2+ T cell (V{delta}2-J{delta}1/2/3/4) abundance was determined by quantitative PCR. Cytokine and chemokine concentrations in sputum were measured. The capacity of bacteria in sputum to produce activating ligands for MAIT cells and V{delta}2+ T cells was inferred by 16S rRNA sequencing.\n\nResultsMAIT cell abundance in sputum was higher in patients with less severe pneumonia; duration of hospital admission was inversely correlated with both MAIT and V{delta}2+ T cell abundance. The abundance of both ILLs was higher in patients with a confirmed bacterial aetiology, however there was no correlation with total bacterial load or the predicted capacity of bacteria to produce activating ligands. Sputum MAIT cell abundance was associated with interferon- , and interferon-{gamma}, and sputum neutrophil abundance, while V{delta}2+ T cell abundance was associated with CXCL11 and interferon-{gamma}.\n\nConclusionsPulmonary MAIT and V{delta}2+ T cells can be detected in sputum in CAP, where they may contribute to improved clinical outcome.

immunology↗

bioRxiv2018

Alternative hydrogen uptake pathways suppress methane production in ruminants

Farmed ruminants are the largest source of anthropogenic methane emissions globally. The methanogenic archaea responsible for these emissions use molecular hydrogen (H2), produced during bacterial and eukaryotic carbohydrate fermentation, as their primary energy source. In this work, we used comparative genomic, metatranscriptomic, and co-culture-based approaches to gain a system-wide understanding of the organisms and pathways responsible for ruminal H2 metabolism. Two thirds of sequenced rumen bacterial and archaeal genomes encode enzymes that catalyze H2 production or consumption, including 26 distinct hydrogenase subgroups. Metatranscriptomic analysis confirmed that these hydrogenases are differentially expressed in sheep rumen. Electron-bifurcating [FeFe]-hydrogenases from carbohydrate-fermenting Clostridia (e.g. Ruminococcus) accounted for half of all hydrogenase transcripts. Various H2 uptake pathways were also expressed, including methanogenesis (Methanobrevibacter), fumarate reduction and nitrate ammonification (Selenomonas), and acetogenesis (Blautia). Whereas methanogenesis predominated in high methane yield sheep, alternative uptake pathways were significantly upregulated in low methane yield sheep. Complementing these findings, we observed significant differential expression and activity of the hydrogenases of the hydrogenogenic cellulose fermenter Ruminococcus albus and the hydrogenotrophic fumarate reducer Wolinella succinogenes in co-culture compared to pure culture. We conclude that H2 metabolism is a more complex and widespread trait among rumen microorganisms than previously recognized. There is evidence that alternative hydrogenotrophs, including acetogens and selenomonads, can prosper in the rumen and effectively compete with methanogens for H2 in low methane yield ruminants. Strategies to increase flux through alternative H2 uptake pathways, including animal selection, dietary supplementation, and methanogenesis inhibitors, may lead to sustained methane mitigation.

microbiology↗

bioRxiv2018

Microbial biogeography of 1,000 geothermal springs in New Zealand

Geothermal springs are model ecosystems to systematically investigate microbial biogeography as they i) represent discrete, homogenous habitats; ii) are abundantly distributed across multiple geographical scales; iii) span broad geochemical gradients; and iv) have simple community structures with reduced metazoan interactions. Taking advantage of these traits, we undertook the largest known consolidated study of geothermal ecosystems (http://1000springs.org.nz) to determine factors that influence biogeographical patterns. Rigorously standardised methodologies were used to measure microbial communities, 46 physicochemical parameters, and metadata from 1,019 hotspring samples across New Zealand. pH was found to be the primary influence on diversity in springs < 70 {degrees}C with community similarity decreasing with geographic distance. Surprisingly, community composition was dominated by two genera (Venenivibrio and Acidithiobacillus) in both average relative abundance (11.2 and 11.1 %) and prevalence (74.2 and 62.9 % respectively) across physicochemical spectrums of 13.9 - 100.6 {degrees}C and pH < 1 - 9.7. This study provides an unprecedented insight into the ecological conditions that drive community assembly in geothermal springs, and can be used as a foundation to improve the characterisation of global microbial biogeographical processes.

microbiology↗

bioRxiv2017

Identifying accurate metagenome and amplicon software via a meta-analysis of benchmarking studies

Environmental DNA sequencing has rapidly become a widely-used technique for investigating a range of questions, particularly related to health and environmental monitoring. There has also been a proliferation of bioinformatic tools for analysing metagenomic and amplicon datasets, which makes selecting adequate tools a significant challenge. A number of benchmark studies have been undertaken; however, these can present conflicting results. We have applied a robust Z-score ranking procedure and a network meta-analysis method to identify software tools that are generally accurate for mapping DNA sequences to taxonomic hierarchies. Based upon these results we have identified some tools and computational strategies that produce robust predictions.

bioinformatics↗