Chao Wu, Fangming Yang, Huanzi Zhong, Jie Hong, Huibin Lin, Mingxi Zong, Huahui Ren, Shaoqian Zhao, Yufei Chen, Zhun Shi, Xingyu Wang, Juan Shen, Qiaoling Wang, Mengshan Ni, Banru Chen, Zhongle Cai, Minchun Zhang, Zhiwen Cao, Kui Wu, Aibo Gao, Junhua Li, Cong Liu, Minfeng Xiao, Yan Li, Juan Shi, Yifei Zhang, Xun Xu, Weiqiong Gu, Yufang Bi, Guang Ning, Weiqing Wang, Jiqiu Wang, Ruixin Liu
Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity...
July 9, 2024: Cell Host & Microbe
Jun Liu, Yong Yang, Fausto Andres Ortiz-Morea, Yulu Zhou, Derui Liu, Yanyan Huang, Jiarui Zheng, Yan Chen, Liang Kong, Zunyong Liu, Dongdong Ge, Mingli Yong, Wenwei Lin, Eugenia Russinova, Libo Shan, Ping He
Plant immune homeostasis is achieved through a balanced immune activation and suppression, enabling effective defense while averting autoimmunity. In Arabidopsis, disrupting a mitogen-activated protein (MAP) kinase cascade triggers nucleotide-binding leucine-rich-repeat (NLR) SUPPRESSOR OF mkk1/2 2 (SUMM2)-mediated autoimmunity. Through an RNAi screen, we identify PUB5, a putative plant U-box E3 ligase, as a critical regulator of SUMM2-mediated autoimmunity. In contrast to typical E3 ligases, PUB5 stabilizes CRCK3, a calmodulin-binding receptor-like cytoplasmic kinase involved in SUMM2 activation...
June 27, 2024: Cell Host & Microbe
Shilan Wang, Yingzhi Liu, Wing Hung Tam, Jessica Y L Ching, Wenye Xu, Shuai Yan, Biyan Qin, Ling Lin, Ye Peng, Jie Zhu, Chun Pan Cheung, Ka Long Ip, Yuen Man Wong, Pui Kuan Cheong, Yuk Ling Yeung, Wing Him Betty Kan, Ting Fan Leung, Tak Yeung Leung, Eugene B Chang, David T Rubin, Erika C Claud, William K K Wu, Hein M Tun, Francis K L Chan, Siew C Ng, Lin Zhang
The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females...
June 27, 2024: Cell Host & Microbe
Haiyuan Shen, Liangliang Zhou, Hao Zhang, Yuanru Yang, Ling Jiang, Dongqing Wu, Hang Shu, Hejiao Zhang, Linxi Xie, Kaichen Zhou, Chen Cheng, Lei Yang, Jiali Jiang, Siya Wang, Yiran Han, Jiayi Zhu, Long Xu, Zhihua Liu, Hua Wang, Shi Yin
The gut microbiota and diet-induced changes in microbiome composition have been linked to various liver diseases, although the specific microbes and mechanisms remain understudied. Alcohol-related liver disease (ALD) is one such disease with limited therapeutic options due to its complex pathogenesis. We demonstrate that a diet rich in soluble dietary fiber increases the abundance of Bacteroides acidifaciens (B. acidifaciens) and alleviates alcohol-induced liver injury in mice. B. acidifaciens treatment alone ameliorates liver injury through a bile salt hydrolase that generates unconjugated bile acids to activate intestinal farnesoid X receptor (FXR) and its downstream target, fibroblast growth factor-15 (FGF15)...
June 25, 2024: Cell Host & Microbe
Tianze Yu, Xiaoqiang Xu, Yang Liu, Xiaokai Wang, Shi Wu, Zhuoqiong Qiu, Xiaochun Liu, Xiaoyu Pan, Chaoying Gu, Shangshang Wang, Lixin Dong, Wei Li, Xu Yao
Cutibacterium acnes is the most abundant bacterium of the human skin microbiome since adolescence, participating in both skin homeostasis and diseases. Here, we demonstrate individual and niche heterogeneity of C. acnes from 1,234 isolate genomes. Skin disease (atopic dermatitis and acne) and body site shape genomic differences of C. acnes, stemming from horizontal gene transfer and selection pressure. C. acnes harbors characteristic metabolic functions, fewer antibiotic resistance genes and virulence factors, and a more stable genome compared with Staphylococcus epidermidis...
June 20, 2024: Cell Host & Microbe
Selene Meza-Perez, Mingyong Liu, Aaron Silva-Sanchez, Casey D Morrow, Peter G Eipers, Elliot J Lefkowitz, Travis Ptacek, Christopher D Scharer, Alexander F Rosenberg, Dave D Hill, Rebecca C Arend, Michael J Gray, Troy D Randall
Gut microbiota influence anti-tumor immunity, often by producing immune-modulating metabolites. However, microbes consume a variety of metabolites that may also impact host immune responses. We show that tumors grow unchecked in the omenta of microbe-replete mice due to immunosuppressive Tregs. By contrast, omental tumors in germ-free, neomycin-treated mice or mice colonized with altered Schaedler's flora (ASF) are spontaneously eliminated by CD8+ T cells. These mice lack Proteobacteria capable of arginine catabolism, causing increases in serum arginine that activate the mammalian target of the rapamycin (mTOR) pathway in Tregs to reduce their suppressive capacity...
June 18, 2024: Cell Host & Microbe
Adarsh Kumbhari, Thomas N H Cheng, Ashwin N Ananthakrishnan, Bharati Kochar, Kristin E Burke, Kevin Shannon, Helena Lau, Ramnik J Xavier, Christopher S Smillie
Gut bacteria are implicated in inflammatory bowel disease (IBD), but the strains driving these associations are unknown. Large-scale studies of microbiome evolution could reveal the imprint of disease on gut bacteria, thus pinpointing the strains and genes that may underlie inflammation. Here, we use stool metagenomes of thousands of IBD patients and healthy controls to reconstruct 140,000 strain genotypes, revealing hundreds of lineages enriched in IBD. We demonstrate that these strains are ancient, taxonomically diverse, and ubiquitous in humans...
June 18, 2024: Cell Host & Microbe
Desmond Richmond-Buccola, Samuel J Hobbs, Jasmine M Garcia, Hunter Toyoda, Jingjing Gao, Sichen Shao, Amy S Y Lee, Philip J Kranzusch
Cyclic oligonucleotide-based signaling system (CBASS) is an antiviral system that protects bacteria from phage infection and is evolutionarily related to human cGAS-STING immunity. cGAS-STING signaling is initiated by the recognition of viral DNA, but the molecular cues activating CBASS are incompletely understood. Using a screen of 975 type I CBASS operon-phage challenges, we show that operons with distinct cGAS/DncV-like nucleotidyltransferases (CD-NTases) and CD-NTase-associated protein (Cap) effectors exhibit marked patterns of phage restriction...
June 17, 2024: Cell Host & Microbe
Lauren A Hesser, Armando A Puente, Jack Arnold, Edward Ionescu, Anjali Mirmira, Nidhi Talasani, Jacqueline Lopez, Lisa Maccio-Maretto, Mark Mimee, Cathryn R Nagler
Depletion of beneficial microbes by modern lifestyle factors correlates with the rising prevalence of food allergies. Re-introduction of allergy-protective bacteria may be an effective treatment strategy. We characterized the fecal microbiota of healthy and food-allergic infants and found that the anaerobe Anaerostipes caccae (A. caccae) was representative of the protective capacity of the healthy microbiota. We isolated a strain of A. caccae from the feces of a healthy infant and identified lactulose as a prebiotic to optimize butyrate production by A...
June 14, 2024: Cell Host & Microbe
Umut Karakus, Ignacio Mena, Jithesh Kottur, Sara S El Zahed, Rocío Seoane, Soner Yildiz, Leanne Chen, Magdalena Plancarte, LeAnn Lindsay, Rebecca Halpin, Timothy B Stockwell, David E Wentworth, Geert-Jan Boons, Florian Krammer, Silke Stertz, Walter Boyce, Robert P de Vries, Aneel K Aggarwal, Adolfo García-Sastre
Avian influenza A virus (IAV) surveillance in Northern California, USA, revealed unique IAV hemagglutinin (HA) genome sequences in cloacal swabs from lesser scaups. We found two closely related HA sequences in the same duck species in 2010 and 2013. Phylogenetic analyses suggest that both sequences belong to the recently discovered H19 subtype, which thus far has remained uncharacterized. We demonstrate that H19 does not bind the canonical IAV receptor sialic acid (Sia). Instead, H19 binds to the major histocompatibility complex class II (MHC class II), which facilitates viral entry...
June 13, 2024: Cell Host & Microbe
Deepto Mozumdar, Andrea Fossati, Erica Stevenson, Jingwen Guan, Eliza Nieweglowska, Sanjana Rao, David Agard, Danielle L Swaney, Joseph Bondy-Denomy
Viral genomes are most vulnerable to cellular defenses at the start of the infection. A family of jumbo phages related to phage ΦKZ, which infects Pseudomonas aeruginosa, assembles a protein-based phage nucleus to protect replicating phage DNA, but how it is protected prior to phage nucleus assembly is unclear. We find that host proteins related to membrane and lipid biology interact with injected phage protein, clustering in an early phage infection (EPI) vesicle. The injected virion RNA polymerase (vRNAP) executes early gene expression until phage genome separation from the vRNAP and the EPI vesicle, moving into the nascent proteinaceous phage nucleus...
June 7, 2024: Cell Host & Microbe
Hannah P Savage, Derek J Bays, Connor R Tiffany, Mariela A F Gonzalez, Eli J Bejarano, Thaynara P Carvalho, Zheng Luo, Hugo L P Masson, Henry Nguyen, Renato L Santos, Krystle L Reagan, George R Thompson, Andreas J Bäumler
Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia...
June 1, 2024: Cell Host & Microbe
Toomas Mets, Tatsuaki Kurata, Karin Ernits, Marcus J O Johansson, Sophie Z Craig, Gabriel Medina Evora, Jessica A Buttress, Roni Odai, Kyo Coppieters't Wallant, Jose A Nakamoto, Lena Shyrokova, Artyom A Egorov, Christopher Ross Doering, Tetiana Brodiazhenko, Michael T Laub, Tanel Tenson, Henrik Strahl, Chloe Martens, Alexander Harms, Abel Garcia-Pino, Gemma C Atkinson, Vasili Hauryliuk
Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored. We identify two Escherichia coli antiphage TAC systems containing host inhibition of growth (HigBA) and CmdTA TA modules, HigBAC and CmdTAC...
May 23, 2024: Cell Host & Microbe
Chaoliang Li, Panrui Zhang, Yadong Xie, Shishan Wang, Meng Guo, Xiaowei Wei, Kaiguang Zhang, Dan Cao, Rongbin Zhou, Sheng Wang, Xinyang Song, Shu Zhu, Wen Pan
Inflammatory bowel disease (IBD) is characterized by dysbiosis of the gut microbiota and dysfunction of intestinal stem cells (ISCs). However, the direct interactions between IBD microbial factors and ISCs are undescribed. Here, we identify α2A -adrenergic receptor (ADRA2A) as a highly expressed GPCR in ISCs. Through PRESTO-Tango screening, we demonstrate that tyramine, primarily produced by Enterococcus via tyrosine decarboxylase (tyrDC), serves as a microbial ligand for ADRA2A. Using an engineered tyrDC-deficient Enterococcus faecalis strain and intestinal epithelial cell-specific Adra2a knockout mice, we show that Enterococcus-derived tyramine suppresses ISC proliferation, thereby impairing epithelial regeneration and exacerbating DSS-induced colitis through ADRA2A...
May 21, 2024: Cell Host & Microbe
Woongjae Yoo, Nicolas G Shealy, Jacob K Zieba, Teresa P Torres, Madi Baltagulov, Julia D Thomas, Catherine D Shelton, Anna G McGovern, Nora J Foegeding, Erin E Olsan, Mariana X Byndloss
Inflammation boosts the availability of electron acceptors in the intestinal lumen, creating a favorable niche for pathogenic Enterobacteriaceae. However, the mechanisms linking intestinal inflammation-mediated changes in luminal metabolites and pathogen expansion remain unclear. Here, we show that mucosal inflammation induced by Salmonella enterica serovar Typhimurium (S. Tm) infection increases intestinal levels of the amino acid aspartate. S. Tm used aspartate-ammonia lyase (aspA)-dependent fumarate respiration for growth in the murine gut only during inflammation...
May 17, 2024: Cell Host & Microbe
Claudia Mirretta Barone, Stacey L Heaver, Lars Gruber, Fabian Zundel, Dai Long Vu, Ruth E Ley
The extent to which bacterial lipids produced by the gut microbiota penetrate host tissues is unclear. Here, we combined mass spectrometry approaches to identify lipids produced by the human gut symbiont Bacteroides thetaiotaomicron (B. theta) and spatially track these bacterial lipids in the mouse colon. We characterize 130 B. theta lipids by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using wild-type and mutant B. theta strains to confidently identify lipid structures and their interconnected pathways in vitro...
May 17, 2024: Cell Host & Microbe
Ariane Amoura, Claire Pistien, Camille Chaligné, Sara Dion, Mélanie Magnan, Antoine Bridier-Nahmias, Alexandra Baron, Françoise Chau, Emmanuel Bourgogne, Minh Le, Erick Denamur, Molly A Ingersoll, Bruno Fantin, Agnès Lefort, Imane El Meouche
Urinary tract infection (UTI), mainly caused by Escherichia coli, are frequent and have a recurrent nature even after antibiotic treatment. Potential bacterial escape mechanisms include growth defects, but probing bacterial division in vivo and establishing its relation to the antibiotic response remain challenging. Using a synthetic reporter of cell division, we follow the temporal dynamics of cell division for different E. coli clinical strains in a UTI mouse model with and without antibiotics. We show that more bacteria are actively dividing in the kidneys and urine compared with the bladder...
May 14, 2024: Cell Host & Microbe
Xuemei Wang, Shuang Zhou, Xiaomin Hu, Chuan Ye, Qixing Nie, Kai Wang, Sen Yan, Jun Lin, Feng Xu, Meng Li, Qing Wu, Lulu Sun, Bo Liu, Yi Zhang, Chuyu Yun, Xian Wang, Huiying Liu, Wen-Bing Yin, Dongyu Zhao, Jing Hang, Shuyang Zhang, Changtao Jiang, Yanli Pang
The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans (C. albicans), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease...
May 13, 2024: Cell Host & Microbe
Joshua B Simpson, Morgan E Walker, Joshua J Sekela, Samantha M Ivey, Parth B Jariwala, Cameron M Storch, Mark E Kowalewski, Amanda L Graboski, Adam D Lietzan, William G Walton, Kacey A Davis, Erica W Cloer, Valentina Borlandelli, Yun-Chung Hsiao, Lee R Roberts, David H Perlman, Xue Liang, Hermen S Overkleeft, Aadra P Bhatt, Kun Lu, Matthew R Redinbo
Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial β-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation...
May 13, 2024: Cell Host & Microbe
Pengcheng Shang, Rita Dos Santos Natividade, Gwen M Taylor, Ankita Ray, Olivia L Welsh, Kay L Fiske, Danica M Sutherland, David Alsteens, Terence S Dermody
Mammalian orthoreovirus (reovirus) is a nonenveloped virus that establishes primary infection in the intestine and disseminates to sites of secondary infection, including the CNS. Reovirus entry involves multiple engagement factors, but how the virus disseminates systemically and targets neurons remains unclear. In this study, we identified murine neuropilin 1 (mNRP1) as a receptor for reovirus. mNRP1 binds reovirus with nanomolar affinity using a unique mechanism of virus-receptor interaction, which is coordinated by multiple interactions between distinct reovirus capsid subunits and multiple NRP1 extracellular domains...
May 8, 2024: Cell Host & Microbe
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