MicrobiomePub Date : 2024-08-08DOI: 10.1186/s40168-024-01866-1
Yi Xiong, Ryan S Mueller, Shichao Feng, Xuan Guo, Chongle Pan
{"title":"Proteomic stable isotope probing with an upgraded Sipros algorithm for improved identification and quantification of isotopically labeled proteins.","authors":"Yi Xiong, Ryan S Mueller, Shichao Feng, Xuan Guo, Chongle Pan","doi":"10.1186/s40168-024-01866-1","DOIUrl":"10.1186/s40168-024-01866-1","url":null,"abstract":"<p><strong>Background: </strong>Proteomic stable isotope probing (SIP) is used in microbial ecology to trace a non-radioactive isotope from a labeled substrate into de novo synthesized proteins in specific populations that are actively assimilating and metabolizing the substrate in a complex microbial community. The Sipros algorithm is used in proteomic SIP to identify variably labeled proteins and quantify their isotopic enrichment levels (atom%) by performing enrichment-resolved database searching.</p><p><strong>Results: </strong>In this study, Sipros was upgraded to improve the labeled protein identification, isotopic enrichment quantification, and database searching speed. The new Sipros 4 was compared with the existing Sipros 3, Calisp, and MetaProSIP in terms of the number of identifications and the accuracy and precision of atom% quantification on both the peptide and protein levels using standard E. coli cultures with 1.07 atom%, 2 atom%, 5 atom%, 25 atom%, 50 atom%, and 99 atom% <sup>13</sup>C enrichment. Sipros 4 outperformed Calisp and MetaProSIP across all samples, especially in samples with ≥ 5 atom% <sup>13</sup>C labeling. The computational speed on Sipros 4 was > 20 times higher than Sipros 3 and was on par with the overall speed of Calisp- and MetaProSIP-based pipelines. Sipros 4 also demonstrated higher sensitivity for the detection of labeled proteins in two <sup>13</sup>C-SIP experiments on a real-world soil community. The labeled proteins were used to trace <sup>13</sup>C from <sup>13</sup>C-methanol and <sup>13</sup>C-labeled plant exudates to the consuming soil microorganisms and their newly synthesized proteins.</p><p><strong>Conclusion: </strong>Overall, Sipros 4 improved the quality of the proteomic SIP results and reduced the computational cost of SIP database searching, which will make proteomic SIP more useful and accessible to the border community. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11313024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-08-07DOI: 10.1186/s40168-024-01857-2
Simon M Gray, Anh D Moss, Jeremy W Herzog, Saori Kashiwagi, Bo Liu, Jacqueline B Young, Shan Sun, Aadra P Bhatt, Anthony A Fodor, R Balfour Sartor
{"title":"Mouse adaptation of human inflammatory bowel diseases microbiota enhances colonization efficiency and alters microbiome aggressiveness depending on the recipient colonic inflammatory environment.","authors":"Simon M Gray, Anh D Moss, Jeremy W Herzog, Saori Kashiwagi, Bo Liu, Jacqueline B Young, Shan Sun, Aadra P Bhatt, Anthony A Fodor, R Balfour Sartor","doi":"10.1186/s40168-024-01857-2","DOIUrl":"10.1186/s40168-024-01857-2","url":null,"abstract":"<p><strong>Background: </strong>Understanding the cause vs consequence relationship of gut inflammation and microbial dysbiosis in inflammatory bowel diseases (IBD) requires a reproducible mouse model of human-microbiota-driven experimental colitis.</p><p><strong>Results: </strong>Our study demonstrated that human fecal microbiota transplant (FMT) transfer efficiency is an underappreciated source of experimental variability in human microbiota-associated (HMA) mice. Pooled human IBD patient fecal microbiota engrafted germ-free (GF) mice with low amplicon sequence variant (ASV)-level transfer efficiency, resulting in high recipient-to-recipient variation of microbiota composition and colitis severity in HMA Il-10<sup>-/-</sup> mice. In contrast, mouse-to-mouse transfer of mouse-adapted human IBD patient microbiota transferred with high efficiency and low compositional variability resulting in highly consistent and reproducible colitis phenotypes in recipient Il-10<sup>-/-</sup> mice. Engraftment of human-to-mouse FMT stochastically varied with individual transplantation events more than mouse-adapted FMT. Human-to-mouse FMT caused a population bottleneck with reassembly of microbiota composition that was host inflammatory environment specific. Mouse-adaptation in the inflamed Il-10<sup>-/-</sup> host reassembled a more aggressive microbiota that induced more severe colitis in serial transplant to Il-10<sup>-/-</sup> mice than the distinct microbiota reassembled in non-inflamed WT hosts.</p><p><strong>Conclusions: </strong>Our findings support a model of IBD pathogenesis in which host inflammation promotes aggressive resident bacteria, which further drives a feed-forward process of dysbiosis exacerbated by gut inflammation. This model implies that effective management of IBD requires treating both the dysregulated host immune response and aggressive inflammation-driven microbiota. We propose that our mouse-adapted human microbiota model is an optimized, reproducible, and rigorous system to study human microbiome-driven disease phenotypes, which may be generalized to mouse models of other human microbiota-modulated diseases, including metabolic syndrome/obesity, diabetes, autoimmune diseases, and cancer. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-08-07DOI: 10.1186/s40168-024-01865-2
Esteban E Nieto, Stephanie D Jurburg, Nicole Steinbach, Sabrina Festa, Irma S Morelli, Bibiana M Coppotelli, Antonis Chatzinotas
{"title":"DNA stable isotope probing reveals the impact of trophic interactions on bioaugmentation of soils with different pollution histories.","authors":"Esteban E Nieto, Stephanie D Jurburg, Nicole Steinbach, Sabrina Festa, Irma S Morelli, Bibiana M Coppotelli, Antonis Chatzinotas","doi":"10.1186/s40168-024-01865-2","DOIUrl":"10.1186/s40168-024-01865-2","url":null,"abstract":"<p><strong>Background: </strong>Bioaugmentation is considered a sustainable and cost-effective methodology to recover contaminated environments, but its outcome is highly variable. Predation is a key top-down control mechanism affecting inoculum establishment, however, its effects on this process have received little attention. This study focused on the impact of trophic interactions on bioaugmentation success in two soils with different pollution exposure histories. We inoculated a <sup>13</sup>C-labelled pollutant-degrading consortium in these soils and tracked the fate of the labelled biomass through stable isotope probing (SIP) of DNA. We identified active bacterial and eukaryotic inoculum-biomass consumers through amplicon sequencing of 16S rRNA and 18S rRNA genes coupled to a novel enrichment factor calculation.</p><p><strong>Results: </strong>Inoculation effectively increased PAH removal in the short-term, but not in the long-term polluted soil. A decrease in the relative abundance of the inoculated genera was observed already on day 15 in the long-term polluted soil, while growth of these genera was observed in the short-term polluted soil, indicating establishment of the inoculum. In both soils, eukaryotic genera dominated as early incorporators of <sup>13</sup>C-labelled biomass, while bacteria incorporated the labelled biomass at the end of the incubation period, probably through cross-feeding. We also found different successional patterns between the two soils. In the short-term polluted soil, Cercozoa and Fungi genera predominated as early incorporators, whereas Ciliophora, Ochrophyta and Amoebozoa were the predominant genera in the long-term polluted soil.</p><p><strong>Conclusion: </strong>Our results showed differences in the inoculum establishment and predator community responses, affecting bioaugmentation efficiency. This highlights the need to further study predation effects on inoculum survival to increase the applicability of inoculation-based technologies. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-08-06DOI: 10.1186/s40168-024-01862-5
Naile Dame-Teixeira, Reem El-Gendy, Andressa Souza de Oliveira, Cleonice Andrade Holanda, Luiz Antonio Soares Romeiro, Thuy Do
{"title":"Engineering a dysbiotic biofilm model for testing root caries interventions through microbial modulation.","authors":"Naile Dame-Teixeira, Reem El-Gendy, Andressa Souza de Oliveira, Cleonice Andrade Holanda, Luiz Antonio Soares Romeiro, Thuy Do","doi":"10.1186/s40168-024-01862-5","DOIUrl":"10.1186/s40168-024-01862-5","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to engineer and optimise a dysbiotic biofilm model to develop in vitro root caries for investigating microbial modulation strategies. The model involved growing complex biofilms from a saliva inoculum collected from four volunteers using two strategies. In the first strategy (\"pre-treatment strategy\"), bovine root slabs were used, and two natural compounds were incorporated at time 0 of the 10-day biofilm experiment, which included sucrose cycles mimicking the cariogenic environment. In the second strategy (\"post-treatment strategy\"), mature biofilms were grown in a modified Calgary biofilm device coated with collagen and hydroxyapatite for 7 days and then were exposed to the same natural compounds. The metatranscriptome of each biofilm was then determined and analysed. Collagenase activity was examined, and the biofilms and dentine were imaged using confocal and scanning electron microscopy (SEM). Mineral loss and lesion formation were confirmed through micro-computed tomography (μ-CT).</p><p><strong>Results: </strong>The pH confirmed the cariogenic condition. In the metatranscriptome, we achieved a biofilm compositional complexity, showing a great diversity of the metabolically active microbiome in both pre- and post-treatment strategies, including reads mapped to microorganisms other than bacteria, such as archaea and viruses. Carbohydrate esterases had increased expression in the post-treated biofilms and in samples without sugar cycles, while glucosyltransferases were highly expressed in the presence of sucrose cycles. Enrichment for functions related to nitrogen compound metabolism and organic cyclic component metabolism in groups without sucrose compared to the sucrose-treated group. Pre-treatment of the roots with cranberry reduced microbial viability and gelatinase (but not collagenase) activity (p < 0.05). SEM images showed the complexity of biofilms was maintained, with a thick extracellular polysaccharides layer.</p><p><strong>Conclusions: </strong>This root caries model was optimized to produce complex cariogenic biofilms and root caries-like lesions, and could be used to test microbial modulation in vitro. Pre-treatments before biofilm development and cariogenic challenges were more effective than post-treatments. The clinical significance lies in the potential to apply the findings to develop varnish products for post-professional tooth prophylaxis, aiming at implementing a strategy for dysbiosis reversal in translational research. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-08-05DOI: 10.1186/s40168-024-01880-3
Cole B Matrishin, Elaine M Haase, Floyd E Dewhirst, Jessica L Mark Welch, Fabiola Miranda-Sanchez, Tsute Chen, Donald C MacFarland, Kathryn M Kauffman
{"title":"Correction: Phages are unrecognized players in the ecology of the oral pathogen Porphyromonas gingivalis.","authors":"Cole B Matrishin, Elaine M Haase, Floyd E Dewhirst, Jessica L Mark Welch, Fabiola Miranda-Sanchez, Tsute Chen, Donald C MacFarland, Kathryn M Kauffman","doi":"10.1186/s40168-024-01880-3","DOIUrl":"10.1186/s40168-024-01880-3","url":null,"abstract":"","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-08-01DOI: 10.1186/s40168-024-01860-7
Alexandra K Stiffler, Poppy J Hesketh-Best, Natascha S Varona, Ashley Zagame, Bailey A Wallace, Brian E Lapointe, Cynthia B Silveira
{"title":"Genomic and induction evidence for bacteriophage contributions to sargassum-bacteria symbioses.","authors":"Alexandra K Stiffler, Poppy J Hesketh-Best, Natascha S Varona, Ashley Zagame, Bailey A Wallace, Brian E Lapointe, Cynthia B Silveira","doi":"10.1186/s40168-024-01860-7","DOIUrl":"10.1186/s40168-024-01860-7","url":null,"abstract":"<p><strong>Background: </strong>Symbioses between primary producers and bacteria are crucial for nutrient exchange that fosters host growth and niche adaptation. Yet, how viruses that infect bacteria (phages) influence these bacteria-eukaryote interactions is still largely unknown. Here, we investigate the role of viruses on the genomic diversity and functional adaptations of bacteria associated with pelagic sargassum. This brown alga has dramatically increased its distribution range in the Atlantic in the past decade and is predicted to continue expanding, imposing severe impacts on coastal ecosystems, economies, and human health.</p><p><strong>Results: </strong>We reconstructed 73 bacterial and 3963 viral metagenome-assembled genomes (bMAGs and vMAGs, respectively) from coastal Sargassum natans VIII and surrounding seawater. S. natans VIII bMAGs were enriched in prophages compared to seawater (28% and 0.02%, respectively). Rhodobacterales and Synechococcus bMAGs, abundant members of the S. natans VIII microbiome, were shared between the algae and seawater but were associated with distinct phages in each environment. Genes related to biofilm formation and quorum sensing were enriched in S. natans VIII phages, indicating their potential to influence algal association in their bacterial hosts. In-vitro assays with a bacterial community harvested from sargassum surface biofilms and depleted of free viruses demonstrated that these bacteria are protected from lytic infection by seawater viruses but contain intact and inducible prophages. These bacteria form thicker biofilms when growing on sargassum-supplemented seawater compared to seawater controls, and phage induction using mitomycin C was associated with a significant decrease in biofilm formation. The induced metagenomes were enriched in genomic sequences classified as temperate viruses compared to uninduced controls.</p><p><strong>Conclusions: </strong>Our data shows that prophages contribute to the flexible genomes of S. natans VIII-associated bacteria. These prophages encode genes with symbiotic functions, and their induction decreases biofilm formation, an essential capacity for flexible symbioses between bacteria and the alga. These results indicate that prophage acquisition and induction contribute to genomic and functional diversification during sargassum-bacteria symbioses, with potential implications for algae growth. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-07-30DOI: 10.1186/s40168-024-01859-0
Petya Koleva, Jia He, Garett Dunsmore, Najmeh Bozorgmehr, Julia Lu, Maia Huynh, Stephanie Tollenaar, Vivian Huang, Jens Walter, Sing Sing Way, Shokrollah Elahi
{"title":"CD71 + erythroid cells promote intestinal symbiotic microbial communities in pregnancy and neonatal period.","authors":"Petya Koleva, Jia He, Garett Dunsmore, Najmeh Bozorgmehr, Julia Lu, Maia Huynh, Stephanie Tollenaar, Vivian Huang, Jens Walter, Sing Sing Way, Shokrollah Elahi","doi":"10.1186/s40168-024-01859-0","DOIUrl":"10.1186/s40168-024-01859-0","url":null,"abstract":"<p><strong>Background: </strong>The establishment of microbial communities in neonatal mammals plays a pivotal role in shaping their immune responses to infections and other immune-related conditions. This process is influenced by a combination of endogenous and exogenous factors. Previously, we reported that depletion of CD71 + erythroid cells (CECs) results in an inflammatory response to microbial communities in newborn mice.</p><p><strong>Results: </strong>Here, we systemically tested this hypothesis and observed that the small intestinal lamina propria of neonatal mice had the highest frequency of CECs during the early days of life. This high abundance of CECs was attributed to erythropoiesis niches within the small intestinal tissues. Notably, the removal of CECs from the intestinal tissues by the anti-CD71 antibody disrupted immune homeostasis. This disruption was evident by alteration in the expression of antimicrobial peptides (AMPs), toll-like receptors (TLRs), inflammatory cytokines/chemokines, and resulting in microbial dysbiosis. Intriguingly, these alterations in microbial communities persisted when tested 5 weeks post-treatment, with a more notable effect observed in female mice. This illustrates a sex-dependent association between CECs and neonatal microbiome modulation. Moreover, we extended our studies on pregnant mice, observing that modulating CECs substantially alters the frequency and diversity of their microbial communities. Finally, we found a significantly lower proportion of CECs in the cord blood of pre-term human newborns, suggesting a potential role in dysregulated immune responses to microbial communities in the gut.</p><p><strong>Conclusions: </strong>Our findings provide novel insights into pivotal role of CECs in immune homeostasis and swift adaptation of microbial communities in newborns. Despite the complexity of the cellular biology of the gut, our findings shed light on the previously unappreciated role of CECs in the dialogue between the microbiota and immune system. These findings have significant implications for human health. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-07-29DOI: 10.1186/s40168-024-01849-2
Xiangyu Zhao, Jiawei Guo, Yiming Wang, Xianfeng Yi
{"title":"High-tannin food enhances spatial memory and scatter-hoarding in rodents via the microbiota-gut-brain axis.","authors":"Xiangyu Zhao, Jiawei Guo, Yiming Wang, Xianfeng Yi","doi":"10.1186/s40168-024-01849-2","DOIUrl":"10.1186/s40168-024-01849-2","url":null,"abstract":"<p><strong>Background: </strong>The mutually beneficial coevolutionary relationships between rodents and plant seeds have been a theme of research in plant-animal relationships. Seed tannins are important secondary metabolites of plants that regulate the food-hoarding behavior of rodents; however, the underlying molecular mechanisms are not yet clear. In this study, we investigated whether and how seed tannins improve spatial memory and regulate the hoarding behavior of Tamias sibiricus by altering their gut microbiota.</p><p><strong>Results: </strong>We showed that acorn tannins not only improved spatial memory but also enhanced scatter-hoarding in T. sibiricus. Changes in the composition and function of the gut microbiota in response to tannins from acorns are closely related to these improvements. Metabonomic analyses revealed the role of gut isovaleric acid and isobutyric acid as well as serum L-tryptophan in mediating the spatial memory of T. sibiricus via the gut microbiota. The hippocampal proteome provides further evidence that the microbiota-gut-brain axis regulates spatial memory and scatter-hoarding in animals. Our study is likely the first to report that plant secondary metabolites improve hippocampal function and spatial memory and ultimately modulate food-hoarding behavior via the microbiota-gut-brain axis.</p><p><strong>Conclusion: </strong>Our findings may have resolved the long-standing puzzle about the hidden role of plant secondary metabolites in manipulating food-hoarding behavior in rodents via the microbiota-gut-brain axis. Our study is important for better understanding the mutualistic coevolution between plants and animals. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-07-29DOI: 10.1186/s40168-024-01858-1
Arno R Bourgonje, Nicolai V Hörstke, Michaela Fehringer, Gabriel Innocenti, Thomas Vogl
{"title":"Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn's disease and chronic fatigue syndrome.","authors":"Arno R Bourgonje, Nicolai V Hörstke, Michaela Fehringer, Gabriel Innocenti, Thomas Vogl","doi":"10.1186/s40168-024-01858-1","DOIUrl":"10.1186/s40168-024-01858-1","url":null,"abstract":"<p><strong>Background: </strong>Elevated systemic antibody responses against gut microbiota flagellins are observed in both Crohn's disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggesting potential serological biomarkers for diagnosis. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) \"stimulator\" and (2) \"silent\" flagellins, which bind TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 (involving a C-terminal domain); (3) \"evader\" flagellins of pathogens, which entirely circumvent TLR5 activation via mutations in the N-terminal TLR5 binding motif.</p><p><strong>Results: </strong>Here, we show that both CD and ME/CFS patients exhibit elevated antibody responses against distinct regions of flagellins compared to healthy individuals. N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling \"stimulator\" and \"silent\" flagellins more than evaders. However, C-terminal antibody-bound flagellins showed a higher resemblance to the stimulator than to silent flagellins in CD, which was not observed in ME/CFS.</p><p><strong>Conclusions: </strong>These findings suggest that antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Blocking this interaction could lead commensal bacteria to be recognized as pathogenic evaders, potentially contributing to dysregulation in both diseases. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between the diseases. Overall, these results highlight the diagnostic potential of these antibody responses and lay a foundation for deeper mechanistic studies of flagellin/TLR5 interactions and their impact on innate/adaptive immunity balance.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicrobiomePub Date : 2024-07-27DOI: 10.1186/s40168-024-01852-7
Lieke J. W. van den Elsen, Akila Rekima, Miriam A. Lynn, Charlotte Isnard, Savannah Machado, Nivedithaa Divakara, Diana Patalwala, Alana Middleton, Natalie Stevens, Florence Servant, Remy Burcelin, David J. Lynn, Valerie Verhasselt
{"title":"Diet at birth is critical for healthy growth, independent of effects on the gut microbiota","authors":"Lieke J. W. van den Elsen, Akila Rekima, Miriam A. Lynn, Charlotte Isnard, Savannah Machado, Nivedithaa Divakara, Diana Patalwala, Alana Middleton, Natalie Stevens, Florence Servant, Remy Burcelin, David J. Lynn, Valerie Verhasselt","doi":"10.1186/s40168-024-01852-7","DOIUrl":"https://doi.org/10.1186/s40168-024-01852-7","url":null,"abstract":"Colostrum is the first milk for a newborn. Its high content in microbiota shaping compounds and its intake at the time of gut microbiota seeding suggests colostrum may be critical in the establishment of a healthy microbiota. There is also accumulating evidence on the importance of the gut microbiota for healthy growth. Here, we aimed to investigate the contribution of colostrum, and colostrum-induced microbiota to growth promotion. Addressing this question is highly significant because (1) globally, less than half of the newborns are fully colostrum fed (2) the evidence for the importance of the microbiota for the prevention of undernutrition has only been demonstrated in juvenile or adult pre-clinical models while stunting already starts before weaning. To address the importance of diet at birth in growth failure, we developed a unique mouse model in which neonates are breastfed by mothers at an advanced stage of lactation who no longer provide colostrum. Feeding newborn mice with mature milk instead of colostrum resulted in significant growth retardation associated with the biological features of chronic undernutrition, such as low leptin levels, dyslipidemia, systemic inflammation, and growth hormone resistance. We next investigated the role of colostrum in microbiota shaping. At the end of the lactation period, we found a major difference in gut microbiota alpha diversity, beta diversity, and taxa distribution in control and colostrum-deprived mice. To determine the causal relationship between changes in microbiota and growth trajectories, we repeated our experiment in germ-free mice. The beneficial effect of colostrum on growth remained in the absence of microbiota. Our data suggest that colostrum may play an important role in the prevention of growth failure. They highlight that the interplay between neonatal gut microbiome assembly and diet may not be as crucial for growth control in the developing newborn as described in young adults. This opens a paradigm shift that will foster research for colostrum’s bioactives that may exert a similar effect to microbiota-derived ligands in promoting growth and lead to new avenues of translational research for newborn-tailored prevention of stunting. ","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":null,"pages":null},"PeriodicalIF":15.5,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141784017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}