Biology subjects

Bang, C.

Publications and source records attributed to Bang, C..

13 recordsLinked to original sources

bioRxiv2025

A metaproteomics-based meta study of samples from patients with inflammatory bowel disease identifies potential markers for diagnosis and therapy monitoring

Inflammatory bowel disease (IBD) is a chronic intestinal disorder involving recurring inflammation and pronounced microbial dysbiosis. Comprehensive studies with large patient cohorts are required to Identify meaningful biomarker candidates for diagnosing and monitoring IBD. In this large-scale meta-study of over 600 samples based on fecal metaproteomics, our goal was to validate known biomarkers and discover new candidates. We performed bioinformatic reanalysis using the Mascot search engine and MMUPHin for batch effect correction as well as knowledge graph-enhanced data analysis. We identified 59 protein groups that varied primarily due to disease, rather than laboratory conditions. These included Alpha-1-acid glycoprotein, which was not reported in the original studies. Of these groups, 53 were differentially abundant in at least one of the two validation datasets. Additionally, 23 of the successfully validated protein groups, primarily from human neutrophil vesicles, were found to be significantly associated with remission during treatment in an independent dataset. This finding suggests their potential for disease monitoring. Validation in other disease contexts, such as non-alcoholic steatohepatitis, diabetes, and colorectal cancer, revealed the necessity of biomarker panels, because individual biomarkers could only distinguish IBD from specific conditions. Our results demonstrate the effectiveness of metaproteomics meta-analyses in discovering and validating biomarker panels and assessing their specificity for IBD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/684320v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@18a6617org.highwire.dtl.DTLVardef@1349adaorg.highwire.dtl.DTLVardef@a27044org.highwire.dtl.DTLVardef@78aabe_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Maternal transmission of a plastid structure enhances offspring fitness

Development in the sea has long been thought to be a nutritional gamble that disproportionately ends in starvation. Here, we unexpectedly show that components of plastids are incorporated into sea urchin eggs and that these, in turn, benefit developmental fitness. We find chromoplast-derived carotenoid crystals and chromoplast-specific metabolites inside of sea urchin eggs. The light-dependent activity of these chromoplast components influence the subsequent abundance of phytohormones that, in turn, regulate the use of energetic lipids that promote development and survival. Offspring that benefit from these chromoplast components are predicted to disperse further, over larger geographic areas, and use a wider range of currents, including those that cross ocean basins. Data presented here challenge the long-held assumption that components of non-metazoan organelles are unable to enter the germline and be passed between generations. We hypothesize that sea urchins manipulate plastids solely for their self-interest by a process that we term machioplasty, with the result of this process being a novel and adaptive form of maternal provisioning. SIGNIFICANCEMaking a fertilizable egg is a complex and carefully regulated process. One long-held assumption is that any component of non-animal organelles are unable to cross the evolutionary valley between non-reproductive and reproductive cells. Here, we unexpectedly show that components of plastids are incorporated into sea urchin eggs and that these, in turn, benefit developmental fitness. Offspring benefit from these plastid components by developing more quickly into larvae and having higher survival due to ability to use phytohormones that influence energetic lipids. This allows offspring to use a wider range of ocean currents, including those that cross entire basins. This challenge the long-held assumption that components of non-metazoan organelles are unable to be passed between generations.

developmental biology↗

bioRxiv2025

Quantifying The Impact of Bulk TCR-Seq Methodological Choices on The Profiled T Cell Repertoire

Bulk T cell repertoire profiling using sequencing (TCR-Seq) is a powerful method to investigate T cell responses to natural infections, vaccines, cancers, and autoimmune diseases. This assay can be conducted using various techniques, such as multiplex PCR or 5-RACE. However, each methods introduces systematic biases that can result in different pictures of the underlying T cell repertoire. Furthermore, the impact of technical variables on the accuracy of these methods remains understudied. Thus, in this study, we systematically characterized different multiplex PCR-based protocols, focusing on the quality and quantity of the utilized RNA/DNA, extraction methods, amplification programs, variations between production batches, and technical handling of samples. Our findings highlight the important role of RNA/DNA quality in shaping the profiling results of T cell repertoires. Whereas low RNA/DNA quantities can be partially compensated for by increasing the number of PCR cycles, this is partially not possible with lower quality. In conclusion, our results highlight the influence of different technical choices on the biological conclusions drawn from TCR-Seq data and provide practical guidelines to finetune these variables to ensure consistent and reliable results under diverse experimental constraints.

immunology↗

bioRxiv2024

Simultaneous Profiling of the Blood and Gut T and B Cell Repertoires in Crohn's Disease and Symptomatic Controls Illustrates Tissue-specific Alterations in the Immune Repertoire of Crohn's Disease Patients

Crohns disease (CD) is a clinical subset of inflammatory bowel disease that is characterized by patchy transmural inflammation across the gastrointestinal tract. Although the exact etiology remains unknown, recent findings suggest that it is a complex multifactorial disease with contributions from the host genetics and environmental factors such as the microbiome. We have shown that the T cell repertoire of CD patients harbors a group of highly expanded T cells which hints toward an antigen-mediated pathology. To profile the immunological signature of CD at a high-resolution we simultaneously profiled the {beta} and {gamma}{delta} T cell repertoire in addition to the B cell repertoire of both the blood and the colonic mucosa for 27 treatment-naive CD patients and 27 age-matched symptomatic controls. Regardless of disease, we observed multiple physiological differences between the immune repertoire of blood and colonic mucosa. Additionally, by comparing the repertoire of CD patients relative to controls, we observed different alterations that were only detected in the blood or colonic mucosa. These include a depletion of mucosal-associated invariant T (MAIT) cells in the blood repertoire, an expansion of TRAV29/DV5-TRAJ5+ clonotypes and a significant depletion of multiple IGHV3-33-IGHJ4+and IGHV3-33-IGHJ6+ clonotypes in the blood and gut IGH repertoire of CD patients. In conclusion, our findings highlight the importance of studying the immune repertoire in a tissue-specific manner and the need to profile the T and B cell immune repertoire of gut tissues.

immunology↗

bioRxiv2023

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia

Horse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum {beta}-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited. Therefore, we collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and ten (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1- V2 gene sequencing. We included 48 samples in the SSG (n=16 horses), 45 in the 5DG (n=15) and 20 in the CG (n=10). Two samples (6.5%) were positive for ESBL-producing Enterobacterales at t0 while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing that horses suffering from acute colic seemed to have a compromised fecal microbiota composition (5DG, SDImean of 5.90; SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0, although the difference lacked significance. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses.

microbiology↗

bioRxiv2023

Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability

Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human hosts metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.

microbiology↗

bioRxiv2023

Comparative metagenomics reveals host-specific functional adaptation of intestinal microbiota across hominids

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we performed high-resolution metagenomic-based analyses of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in humans populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer new and exciting insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids, demonstrating that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.

evolutionary biology↗

bioRxiv2022

The effects of ethnoracial-related stressors during pregnancy on the developing offspring brain.

We are increasingly aware of the effects of ethnoracial stress on health, with emerging interest in the potential for intergenerational transmission before birth. Here, we investigate the effect of maternal prenatal discrimination and acculturation experiences on fetal growth, birth outcomes, and functional connectivity in the infant brain. In pregnant adolescent women, we collected self-report measures of acculturation (tailored to an adolescent and Latinx population), discrimination, and maternal distress (i.e., stress and depressive symptoms; n=165). Fetal growth were obtained via electronic health records (n=92), and infant amygdala seed connectivity was assessed using functional magnetic resonance imaging (n=38). We found that greater maternal prenatal assimilation to the host culture was associated with slower fetal growth, lower gestational age at birth, and weaker amygdala-fusiform connectivity. Maternal prenatal discrimination was associated with weaker amygdala-prefrontal connectivity. Together, these results suggest intergenerational effects of ethnoracial stressors on the growth and neural development of future generations.

neuroscience↗

bioRxiv2021

Microcin MccI47 selectively inhibits enteric bacteria and reduces carbapenem-resistant Klebsiella pneumoniae colonization in vivo when administered via an engineered live biotherapeutic

BackgroundThe gastrointestinal (GI) tract is the reservoir for multidrug-resistant (MDR) pathogens, specifically carbapenem-resistant (CR) Klebsiella pneumoniae and other Enterobacteriaceae, which often lead to the spread of antimicrobial resistance genes, severe extraintestinal infections, and lethal outcomes. Selective GI decolonization has been proposed as a new strategy for preventing transmission to other body sites and minimizing spreading to susceptible individuals. ResultsHere, we purify the to-date uncharacterized class IIb microcin I47 (MccI47) and demonstrate potent inhibition of numerous Enterobacteriaceae, including multidrug-resistant clinical isolates, in vitro at concentrations resembling those of commonly prescribed antibiotics. We then genetically modify the probiotic bacterium Escherichia coli Nissle 1917 (EcN) to produce MccI47 from a stable multicopy plasmid by using MccI47 toxin production in a counterselection mechanism to engineer one of the native EcN plasmids, which renders provisions for inducible expression and plasmid selection unnecessary. We then test the clinical relevance of the MccI47-producing engineered EcN in a murine CR K. pneumoniae colonization model and demonstrate significant MccI47-dependent reduction of CR K. pneumoniae abundance after seven days of daily oral live biotherapeutic administration without disruption of the resident microbiota. ConclusionsThis study provides the first demonstration of MccI47 as a potent antimicrobial against certain Enterobacteriaceae, and its ability to significantly reduce the abundance of CR K. pneumoniae in a preclinical animal model, when delivered from an engineered live biotherapeutic product. This study serves as the foundational step towards the use of engineered live biotherapeutic products aimed at the selective removal of MDR pathogens from the GI tract

bioengineering↗

bioRxiv2021

Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in PSC.

ObjectiveConflicting microbiota data exist for primary sclerosing cholangitis (PSC) and experimental models. Goal: Define complex interactions between resident microbes and their association in PSC patients by studying antibiotic-treated specific pathogen-free (SPF) and germ-free (GF) multi-drug-resistant 2 deficient (mdr2-/-) mice. DesignWe measured weights, liver enzymes, RNA expression, histological, immunohistochemical and fibrotic biochemical parameters, fecal 16s rRNA gene profiling, and metabolomic endpoints in gnotobiotic and antibiotic-treated SPF mdr2-/- mice and targeted metagenomic analysis in PSC patients. ResultsGF mdr2-/- mice had exaggerated hepatic inflammation and fibrosis with 100% mortality by 8 weeks; early SPF autologous stool transplantation rescued liver-related mortality. Broad-spectrum antibiotics and vancomycin alone accelerated disease in weanling SPF mdr2-/- mice, indicating that vancomycin-sensitive resident microbiota protect against hepatobiliary disease. Vancomycin treatment selectively decreased Lachnospiraceae and short-chain fatty acids (SCFAs) but expanded Enterococcus and Enterobacteriaceae. Antibiotics increased cytolysin-expressing E. faecalis and E. coli liver translocation; colonization of gnotobiotic mdr2-/- mice with translocated E. faecalis and E. coli strains accelerated liver inflammation and mortality. Lachnospiraceae colonization of antibiotic pre-treated mdr2-/- mice reduced liver fibrosis, inflammation and translocation of pathobionts, while Lachnospiraceae-produced SCFA decreased fibrosis. Fecal E. faecalis/ Enterobacteriaceae was positively and Lachnospiraceae was negatively associated with PSC patients clinical severity Mayo risk scores. ConclusionsWe identified specific functionally protective and detrimental resident bacterial species in mdr2-/- mice and PSC patients with associated clinical outcomes. These insights may guide personalized targeted therapeutic interventions in PSC patients.

microbiology↗

bioRxiv2020

Genetics of human gut microbiome composition

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 out of 410 genera were detected in more than 95% samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 31 loci affecting microbiome at a genome-wide significant (P<5x10-8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (GWAS signal P=1.28x10-20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95x10-10<P<5x10-8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome has causal effects in ulcerative colitis and rheumatoid arthritis.

genetics↗

bioRxiv2020

Histone variants in archaea and the evolution of combinatorial chromatin complexity

Nucleosomes in eukaryotes act as platforms for the dynamic integration of epigenetic information. Post-translational modifications are reversibly added or removed and core histones exchanged for paralogous variants, in concert with changing demands on transcription and genome accessibility. Histones are also common in archaea. Their role in genome regulation, however, and the capacity of individual paralogs to assemble into histone-DNA complexes with distinct properties remain poorly understood. Here, we combine structural modelling with phylogenetic analysis to shed light on archaeal histone paralogs, their evolutionary history and capacity to generate complex combinatorial chromatin states through hetero-oligomeric assembly. Focusing on the human commensal Methanosphaera stadtmanae as a model archaeal system, we show that the heteromeric complexes that can be assembled from its seven histone paralogs vary substantially in DNA binding affinity and tetramer stability, occupying a large but densely populated chromatin state space. Using molecular dynamics simulations, we go on to identify unique paralogs in M. stadtmanae and Methanobrevibacter smithii that are characterized by unstable dimer:dimer interfaces. We propose that these paralogs act as capstones that prevent stable tetramer formation and extension into longer oligomers characteristic of model archaeal histones. Importantly, we provide evidence from phylogeny and genome architecture that these capstones, as well as other paralogs in the Methanobacteriales, have been maintained for hundreds of millions of years following ancient duplication events. Taken together, our findings indicate that at least some archaeal histone paralogs have evolved to play distinct and conserved functional roles, reminiscent of eukaryotic histone variants. We conclude that combinatorially complex histone-based chromatin is not restricted to eukaryotes and likely predates their emergence.

evolutionary biology↗

bioRxiv2020

Primate phageomes are structured by superhost phylogeny and environment

The evolutionary origins of human-associated bacteriophage communities are poorly understood. To address this question, we examined fecal phageomes of 23 wild non-human primate taxa, including multiple representatives of all the major primate radiations, and find relatives of the majority of human-associated phages. Primate taxa have distinct phageome compositions that exhibit a clear phylosymbiotic signal, and phage-superhost co-divergence is detected for 44 individual phages. Within species, neighboring social groups harbor evolutionarily and compositionally distinct phageomes, structured by superhost social behavior. However, captive non-human primate phageomes are more similar to humans than their wild counterparts, revealing replacement of wild-associated phages with human-associated ones. Together, our results suggest that potentially labile primate-phage associations persisted across millions of years of evolution, potentially facilitated by transmission between groupmates. One Sentence SummaryRelatives of human-associated phages in wild primates reveal ancient but dynamic superhost-phage associations shaped by social transmission.

microbiology↗