Laura M Cox, Amir Hadi Maghzi, Shirong Liu, Stephanie K Tankou, Fyonn H Dhang, Valerie Willocq, Anya Song, Caroline Wasén, Shahamat Tauhid, Renxin Chu, Mark C Anderson, Philip L De Jager, Mariann Polgar-Turcsanyi, Brian C Healy, Bonnie I Glanz, Rohit Bakshi, Tanuja Chitnis, and Howard L Weiner. 2021. “Gut Microbiome in Progressive Multiple Sclerosis.” Ann Neurol, 89, 6, Pp. 1195-1211.Abstract
OBJECTIVE: This study was undertaken to investigate the gut microbiome in progressive multiple sclerosis (MS) and how it relates to clinical disease. METHODS: We sequenced the microbiota from healthy controls and relapsing-remitting MS (RRMS) and progressive MS patients and correlated the levels of bacteria with clinical features of disease, including Expanded Disability Status Scale (EDSS), quality of life, and brain magnetic resonance imaging lesions/atrophy. We colonized mice with MS-derived Akkermansia and induced experimental autoimmune encephalomyelitis (EAE). RESULTS: Microbiota β-diversity differed between MS patients and controls but did not differ between RRMS and progressive MS or differ based on disease-modifying therapies. Disease status had the greatest effect on the microbiome β-diversity, followed by body mass index, race, and sex. In both progressive MS and RRMS, we found increased Clostridium bolteae, Ruthenibacterium lactatiformans, and Akkermansia and decreased Blautia wexlerae, Dorea formicigenerans, and Erysipelotrichaceae CCMM. Unique to progressive MS, we found elevated Enterobacteriaceae and Clostridium g24 FCEY and decreased Blautia and Agathobaculum. Several Clostridium species were associated with higher EDSS and fatigue scores. Contrary to the view that elevated Akkermansia in MS has a detrimental role, we found that Akkermansia was linked to lower disability, suggesting a beneficial role. Consistent with this, we found that Akkermansia isolated from MS patients ameliorated EAE, which was linked to a reduction in RORγt+ and IL-17-producing γδ T cells. INTERPRETATION: Whereas some microbiota alterations are shared in relapsing and progressive MS, we identified unique bacteria associated with progressive MS and clinical measures of disease. Furthermore, elevated Akkermansia in MS may be a compensatory beneficial response in the MS microbiome. ANN NEUROL 2021;89:1195-1211.
Thais G Moreira, Davide Mangani, Laura M Cox, Jeffrey Leibowitz, Eduardo LC Lobo, Mariana A Oliveira, Christian D Gauthier, Brenda N Nakagaki, Valerie Willocq, Anya Song, Lydia Guo, David CA Lima, Gopal Murugaiyan, Oleg Butovsky, Galina Gabriely, Ana C Anderson, Rafael M Rezende, Ana Maria C Faria, and Howard L Weiner. 2021. “PD-L1 and XCR1 dendritic cells are region-specific regulators of gut homeostasis.” Nat Commun, 12, 1, Pp. 4907.Abstract
The intestinal mucosa constitutes an environment of closely regulated immune cells. Dendritic cells (DC) interact with the gut microbiome and antigens and are important in maintaining gut homeostasis. Here, we investigate DC transcriptome, phenotype and function in five anatomical locations of the gut lamina propria (LP) which constitute different antigenic environments. We show that DC from distinct gut LP compartments induce distinct T cell differentiation and cytokine secretion. We also find that PD-L1+ DC in the duodenal LP and XCR1+ DC in the colonic LP comprise distinct tolerogenic DC subsets that are crucial for gut homeostasis. Mice lacking PD-L1+ and XCR1+ DC have a proinflammatory gut milieu associated with an increase in Th1/Th17 cells and a decrease in Treg cells and have exacerbated disease in the models of 5-FU-induced mucositis and DSS-induced colitis. Our findings identify PD-L1+ and XCR1+ DC as region-specific physiologic regulators of intestinal homeostasis.
Panayota Kolypetri, Shirong Liu, Laura M Cox, Mai Fujiwara, Radhika Raheja, Dvora Ghitza, Anya Song, Dominique Daatselaar, Valerie Willocq, and Howard L Weiner. 2021. “Regulation of splenic monocyte homeostasis and function by gut microbial products.” iScience, 24, 4, Pp. 102356.Abstract
Splenic Ly6Chigh monocytes are innate immune cells involved in the regulation of central nervous system-related diseases. Recent studies have reported the shaping of peripheral immune responses by the gut microbiome via mostly unexplored pathways. In this study, we report that a 4-day antibiotic treatment eliminates certain families of the Bacteroidetes, Firmicutes, Tenericutes, and Actinobacteria phyla in the gut and reduces the levels of multiple pattern recognition receptor (PRR) ligands in the serum. Reduction of PRR ligands was associated with reduced numbers and perturbed function of splenic Ly6Chigh monocytes, which acquired an immature phenotype producing decreased levels of inflammatory cytokines and exhibiting increased phagocytic and anti-microbial abilities. Addition of PRR ligands in antibiotic-treated mice restored the number and functions of splenic Ly6Chigh monocytes. Our data identify circulating PRR ligands as critical regulators of the splenic Ly6Chigh monocyte behavior and suggest possible intervention pathways to manipulate this crucial immune cell subset.
Benjamin M Scott, Cristina Gutiérrez-Vázquez, Liliana M Sanmarco, Jessica A da Silva Pereira, Zhaorong Li, Agustín Plasencia, Patrick Hewson, Laura M Cox, Madelynn O'Brien, Steven K Chen, Pedro M Moraes-Vieira, Belinda SW Chang, Sergio G Peisajovich, and Francisco J Quintana. 2021. “Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease.” Nat Med, 27, 7, Pp. 1212-1222.Abstract
Inflammatory bowel disease (IBD) is a complex chronic inflammatory disorder of the gastrointestinal tract. Extracellular adenosine triphosphate (eATP) produced by the commensal microbiota and host cells activates purinergic signaling, promoting intestinal inflammation and pathology. Based on the role of eATP in intestinal inflammation, we developed yeast-based engineered probiotics that express a human P2Y2 purinergic receptor with up to a 1,000-fold increase in eATP sensitivity. We linked the activation of this engineered P2Y2 receptor to the secretion of the ATP-degrading enzyme apyrase, thus creating engineered yeast probiotics capable of sensing a pro-inflammatory molecule and generating a proportional self-regulated response aimed at its neutralization. These self-tunable yeast probiotics suppressed intestinal inflammation in mouse models of IBD, reducing intestinal fibrosis and dysbiosis with an efficacy similar to or higher than that of standard-of-care therapies usually associated with notable adverse events. By combining directed evolution and synthetic gene circuits, we developed a unique self-modulatory platform for the treatment of IBD and potentially other inflammation-driven pathologies.
Lekha Pandit, Laura M Cox, Chaithra Malli, Anitha D'Cunha, Timothy Rooney, Hrishikesh Lokhande, Valerie Willocq, Shrishti Saxena, and Tanuja Chitnis. 2020. “Clostridium bolteae is elevated in neuromyelitis optica spectrum disorder in India and shares sequence similarity with AQP4.” Neurology-Neuroimmunology Neuroinflammation, 8, 1.
Laura M Cox and Howard L Weiner. 2020. “The microbiome requires a genetically susceptible host to induce central nervous system autoimmunity.” Proceedings of the National Academy of Sciences, 117, 45, Pp. 27764-27766.
Laura M Cox, Marissa J Schafer, Jiho Sohn, Julia Vincentini, Howard L Weiner, Stephen D Ginsberg, and Martin J Blaser. 2019. “Calorie restriction slows age-related microbiota changes in an Alzheimer's disease model in female mice.” Sci Rep, 9, 1, Pp. 17904.Abstract
Alzheimer's disease (AD) affects an estimated 5.8 million Americans, and advanced age is the greatest risk factor. AD patients have altered intestinal microbiota. Accordingly, depleting intestinal microbiota in AD animal models reduces amyloid-beta (Aβ) plaque deposition. Age-related changes in the microbiota contribute to immunologic and physiologic decline. Translationally relevant dietary manipulations may be an effective approach to slow microbiota changes during aging. We previously showed that calorie restriction (CR) reduced brain Aβ deposition in the well-established Tg2576 mouse model of AD. Presently, we investigated whether CR alters the microbiome during aging. We found that female Tg2576 mice have more substantial age-related microbiome changes compared to wildtype (WT) mice, including an increase in Bacteroides, which were normalized by CR. Specific gut microbiota changes were linked to Aβ levels, with greater effects in females than in males. In the gut, Tg2576 female mice had an enhanced intestinal inflammatory transcriptional profile, which was reversed by CR. Furthermore, we demonstrate that Bacteroides colonization exacerbates Aβ deposition, which may be a mechanism whereby the gut impacts AD pathogenesis. These results suggest that long-term CR may alter the gut environment and prevent the expansion of microbes that contribute to age-related cognitive decline.
Hannah Fehlner-Peach, Cara Magnabosco, Varsha Raghavan, Jose U Scher, Adrian Tett, Laura M Cox, Claire Gottsegen, Aaron Watters, John D Wiltshire-Gordon, Nicola Segata, Richard Bonneau, and Dan R Littman. 2019. “Distinct Polysaccharide Utilization Profiles of Human Intestinal Prevotella copri Isolates.” Cell Host Microbe, 26, 5, Pp. 680-690.e5.Abstract
Gut-dwelling Prevotella copri (P. copri), the most prevalent Prevotella species in the human gut, have been associated with diet and disease. However, our understanding of their diversity and function remains rudimentary because studies have been limited to 16S and metagenomic surveys and experiments using a single type strain. Here, we describe the genomic diversity of 83 P. copri isolates from 11 human donors. We demonstrate that genomically distinct isolates, which can be categorized into different P. copri complex clades, utilize defined sets of polysaccharides. These differences are exemplified by variations in susC genes involved in polysaccharide transport as well as polysaccharide utilization loci (PULs) that were predicted in part from genomic and metagenomic data. Functional validation of these PULs showed that P. copri isolates utilize distinct sets of polysaccharides from dietary plant, but not animal, sources. These findings reveal both genomic and functional differences in polysaccharide utilization across human intestinal P. copri strains.
Shawon Lahiri, Hyejin Kim, Isabel Garcia-Perez, Musarrat Maisha Reza, Katherine A Martin, Parag Kundu, Laura M Cox, Joel Selkrig, Joram M Posma, Hongbo Zhang, Parasuraman Padmanabhan, Catherine Moret, Balázs Gulyás, Martin J Blaser, Johan Auwerx, Elaine Holmes, Jeremy Nicholson, Walter Wahli, and Sven Pettersson. 2019. “The gut microbiota influences skeletal muscle mass and function in mice.” Sci Transl Med, 11, 502.Abstract
The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes and Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.
Carlos G Gonzalez, Stephanie K Tankou, Laura M Cox, Ellen P Casavant, Howard L Weiner, and Joshua E Elias. 2019. “Latent-period stool proteomic assay of multiple sclerosis model indicates protective capacity of host-expressed protease inhibitors.” Sci Rep, 9, 1, Pp. 12460.Abstract
Diseases are often diagnosed once overt symptoms arise, ignoring the prior latent period when effective prevention may be possible. Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, exhibits such disease latency, but the molecular processes underlying this asymptomatic period remain poorly characterized. Gut microbes also influence EAE severity, yet their impact on the latent period remains unknown. Here, we show the latent period between immunization and EAE's overt symptom onset is characterized by distinct host responses as measured by stool proteomics. In particular, we found a transient increase in protease inhibitors that inversely correlated with disease severity. Vancomycin administration attenuated both EAE symptoms and protease inhibitor induction potentially by decreasing immune system reactivity, supporting a subset of the microbiota's role in modulating the host's latent period response. These results strengthen previous evidence of proteases and their inhibitors in EAE and highlight the utility stool-omics for revealing complex, dynamic biology.
Shirong Liu, Rafael M Rezende, Thais G Moreira, Stephanie K Tankou, Laura M Cox, Meng Wu, Anya Song, Fyonn H Dhang, Zhiyun Wei, Gianluca Costamagna, and Howard L Weiner. 2019. “Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila.” Cell Host Microbe, 26, 6, Pp. 779-794.e8.Abstract
Fecal transfer from healthy donors is being explored as a microbiome modality. MicroRNAs (miRNAs) have been found to affect the microbiome. Multiple sclerosis (MS) patients have been shown to have an altered gut microbiome. Here, we unexpectedly found that transfer of feces harvested at peak disease from the experimental autoimmune encephalomyelitis (EAE) model of MS ameliorates disease in recipients in a miRNA-dependent manner. Specifically, we show that miR-30d is enriched in the feces of peak EAE and untreated MS patients. Synthetic miR-30d given orally ameliorates EAE through expansion of regulatory T cells (Tregs). Mechanistically, miR-30d regulates the expression of a lactase in Akkermansia muciniphila, which increases Akkermansia abundance in the gut. The expanded Akkermansia in turn increases Tregs to suppress EAE symptoms. Our findings report the mechanistic underpinnings of a miRNA-microbiome axis and suggest that the feces of diseased subjects might be enriched with miRNAs with therapeutic properties.
Laura M Cox, Hadi Abou-El-Hassan, Amir Hadi Maghzi, Julia Vincentini, and Howard L Weiner. 2019. “The sex-specific interaction of the microbiome in neurodegenerative diseases.” Brain Res, 1724, Pp. 146385.Abstract
Several neurologic diseases exhibit different prevalence and severity in males and females, highlighting the importance of understanding the influence of biologic sex and gender. Beyond host-intrinsic differences in neurologic development and homeostasis, evidence is now emerging that the microbiota is an important environmental factor that may account for differences between men and women in neurologic disease. The gut microbiota is composed of trillions of bacteria, archaea, viruses, and fungi, that can confer benefits to the host or promote disease. There is bidirectional communication between the intestinal microbiota and the brain that is mediated via immunologic, endocrine, and neural signaling pathways. While there is substantial interindividual variation within the microbiota, differences between males and females can be detected. In animal models, sex-specific microbiota differences can affect susceptibility to chronic diseases. In this review, we discuss the ways in which neurologic diseases may be regulated by the microbiota in a sex-specific manner.
Stephen J Rubino, Lior Mayo, Isabella Wimmer, Victoria Siedler, Florian Brunner, Simon Hametner, Asaf Madi, Amanda Lanser, Thais Moreira, Dustin Donnelly, Laura Cox, Rafael Machado Rezende, Oleg Butovsky, Hans Lassmann, and Howard L Weiner. 2018. “Acute microglia ablation induces neurodegeneration in the somatosensory system.” Nat Commun, 9, 1, Pp. 4578.Abstract
Previous studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation in the long-term state of the CNS environment has not been characterized. Here, we report that acute and synchronous microglia depletion and subsequent repopulation induces gray matter microgliosis, neuronal death in the somatosensory cortex and ataxia-like behavior. We find a type 1 interferon inflammatory signature in degenerating somatosensory cortex from microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type 1 interferon-driven inflammation, restore microglia homeostasis and reduce ataxic behavior. Neither microglia depletion nor repopulation impact neuropathology or T-cell responses during experimental autoimmune encephalomyelitis. Together, we found that acute microglia ablation induces a type 1 interferon activation state of gray matter microglia associated with acute neurodegeneration.
Anjelique F Schulfer, Thomas Battaglia, Yelina Alvarez, Luc Bijnens, Victoria E Ruiz, Melody Ho, Serina Robinson, Tonya Ward, Laura M Cox, Arlin B Rogers, Dan Knights, Balfour R Sartor, and Martin J Blaser. 2018. “Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice.” Nat Microbiol, 3, 2, Pp. 234-242.Abstract
Antibiotic exposure in children has been associated with the risk of inflammatory bowel disease (IBD). Antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, so we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild-type mothers, we showed that both inoculum and genotype shape microbiota populations in the offspring. Because IL10 mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10 offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to the offspring, with both ecological and long-term disease consequences.
Stephanie K Tankou, Keren Regev, Brian C Healy, Laura M Cox, Emily Tjon, Pia Kivisakk, Isabelle P Vanande, Sandra Cook, Roopali Gandhi, Bonnie Glanz, James Stankiewicz, and Howard L Weiner. 2018. “Investigation of probiotics in multiple sclerosis.” Mult Scler, 24, 1, Pp. 58-63.Abstract
None of the disease-modifying therapies (DMTs) currently being used for the management of multiple sclerosis (MS) are 100% effective. In addition, side effects associated with the use of these DMTs have limited the practice of combination therapy. Hence, there is a need for safe immunomodulatory agents to fine-tune the management of MS. The gut microbiome plays an important role in autoimmunity, and several studies have reported alterations in the gut microbiome of MS patients. Studies in animal model of MS have identified members of the gut commensal microflora that exacerbate or ameliorate neuroinflammation. Probiotics represent an oral, non-toxic immunomodulatory agent that could be used in combination with current MS therapy. We designed a pilot study to investigate the effect of VSL3 on the gut microbiome and peripheral immune system function in healthy controls and MS patients. VSL3 administration was associated with increased abundance of many taxa with enriched taxa predominated by Lactobacillus, Streptococcus, and Bifidobacterium species. At the immune level, VSL3 administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of intermediate monocytes (CD14CD16), decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes as well as decreased human leukocyte antigen-antigen D related (HLA-DR) MFI on dendritic cells.
Laura M Cox and Howard L Weiner. 2018. “Microbiota Signaling Pathways that Influence Neurologic Disease.” Neurotherapeutics, 15, 1, Pp. 135-145.Abstract
Though seemingly distinct and autonomous, emerging evidence suggests there is a bidirectional interaction between the intestinal microbiota and the brain. This crosstalk may play a substantial role in neurologic diseases, including anxiety, depression, autism, multiple sclerosis, Parkinson's disease, and, potentially, Alzheimer's disease. Long hypothesized by Metchnikoff and others well over 100 years ago, investigations into the mind-microbe axis is now seeing a rapid resurgence of research. If specific pathways and mechanisms of interaction are understood, it could have broad therapeutic potential, as the microbiome is environmentally acquired and can be modified to promote health. This review will discuss immune, endocrine, and neural system pathways that interconnect the gut microbiota to central nervous system and discuss how these findings might be applied to neurologic disease.
Stephanie K Tankou, Keren Regev, Brian C Healy, Emily Tjon, Luca Laghi, Laura M Cox, Pia Kivisäkk, Isabelle V Pierre, Lokhande Hrishikesh, Roopali Gandhi, Sandra Cook, Bonnie Glanz, James Stankiewicz, and Howard L Weiner. 2018. “A probiotic modulates the microbiome and immunity in multiple sclerosis.” Ann Neurol, 83, 6, Pp. 1147-1161.Abstract
OBJECTIVE: Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (MS) patients. METHODS: MS patients (N = 9) and controls (N = 13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus twice-daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics. RESULTS: Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS, including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients, such as methane metabolism, following probiotic supplementation. At the immune level, probiotic administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes, as well as decreased human leukocyte antigen (HLA) D related MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic-induced increase in abundance of Lactobacillus and Bifidobacterium was associated with decreased expression of MS risk allele HLA.DPB1 in controls. INTERPRETATION: Our results suggest that probiotics could have a synergistic effect with current MS therapies. Ann Neurol 2018.
Laura Llorca, Guillermo Pérez-Pérez, Pedro Urruzuno, Maria Josefa Martinez, Tadasu Iizumi, Zhan Gao, Jiho Sohn, Jennifer Chung, Laura Cox, Aurea Simón-Soro, Alex Mira, and Teresa Alarcón. 2017. “Characterization of the Gastric Microbiota in a Pediatric Population According to Helicobacter pylori Status.” Pediatr Infect Dis J, 36, 2, Pp. 173-178.Abstract
BACKGROUND: Helicobacter pylori colonizes the human stomach of approximately 50% of the world's population, and increases the risk of several gastric diseases. The goal of this study is to compare the gastric microbiota in pediatric patients with and without H. pylori colonization. METHODS: We studied 51 children who underwent gastric endoscopy because of dyspeptic symptoms (18 H. pylori positive and 33 negative). Gastric biopsies were obtained for rapid urease test, culture, histology and DNA extraction. H. pylori was quantified by quantitative polymerase chain reaction and the gastric microbiome studied by V4-16S ribosomal RNA gene high-throughput sequencing. RESULTS: Bacterial richness and diversity of H. pylori-positive specimens were lower than those of negative, and both groups were clearly separated according to beta diversity. Taxonomic analysis confirmed that H. pylori-positive subjects had a higher relative abundance of Helicobacter genus (66.3%) than H. pylori-negative subjects (0.45%). Four phyla (proteobacteria, bacteroidetes, firmicutes and actinobacteria) accounted for >97% of all reads in both groups. Within proteobacteria, gamma- and betaproteobacteria were the most abundant for H. pylori-negative patients, whereas epsilonproteobacteria was for H. pylori positive. H. pylori-positive patients were associated with low body mass index. In the group of underweight patients (body mass index, <18.5), there were 46.1% of H. pylori-positive patients compared with 24% in the nonunderweight group (P = 0.049). Patients with active superficial gastritis in H. pylori-positive patients had the lowest alpha diversity (P = 0.035). CONCLUSIONS: We characterized the gastric microbiota for the first time in children with and without H. pylori and observed that when H. pylori is present, it tends to dominate the microbial community. In the H. pylori-negative patients, there was more relative abundance of gammaproteobacteria, betaproteobacteria, bacteroidia and clostridia classes and a higher bacterial richness and diversity.
Laura M Cox, Jiho Sohn, Kerin L Tyrrell, Diane M Citron, Paul A Lawson, Nisha B Patel, Tadasu Iizumi, Guillermo I Perez-Perez, Ellie JC Goldstein, and Martin J Blaser. 2017. “Corrigendum: Description of two novel members of the family Erysipelotrichaceae: Ileibacterium valens gen. nov., sp. nov. and Dubosiella newyorkensis, gen. nov., sp. nov., from the murine intestine, and emendation to the description of Faecalibacterium ro.” Int J Syst Evol Microbiol, 67, 10, Pp. 4289.
Laura M Cox, Jiho Sohn, Kerin L Tyrrell, Diane M Citron, Paul A Lawson, Nisha B Patel, Tadasu Iizumi, Guillermo I Perez-Perez, Ellie JC Goldstein, and Martin J Blaser. 2017. “Description of two novel members of the family Erysipelotrichaceae: Ileibacterium valens gen. nov., sp. nov. and Dubosiella newyorkensis, gen. nov., sp. nov., from the murine intestine, and emendation to the description of Faecalibaculum rodentium.” Int J Syst Evol Microbiol, 67, 5, Pp. 1247-1254.Abstract
To better characterize murine intestinal microbiota, a large number (187) of Gram-positive-staining, rod- and coccoid-shaped, and facultatively or strictly anaerobic bacteria were isolated from small and large intestinal contents from mice. Based on 16S rRNA gene sequencing, a total 115 isolates formed three phylogenetically distinct clusters located within the family Erysipelotrichaceae. Group 1, as represented by strain NYU-BL-A3T, was most closely related to Allobaculum stercoricanis, with 16S rRNA gene sequence similarity values of 87.7 %. A second group, represented by NYU-BL-A4T, was most closely related to Faecalibaculum rodentium, with 86.6 % 16S rRNA gene sequence similarity. A third group had a nearly identical 16S rRNA gene sequence (99.9 %) compared with the recently described Faecalibaculum rodentium, also recovered from a laboratory mouse; however, this strain had a few differences in biochemical characteristics, which are detailed in an emended description. The predominant (>10 %) cellular fatty acids of strain NYU-BL-A3T were C16 : 0 and C18 : 0, and those of strain NYU-BL-A4T were C10 : 0, C16 : 0, C18 : 0 and C18 : 1ω9c. The two groups could also be distinguished by multiple biochemical reactions, with the group represented by NYU-BL-A4T being considerably more active. Based on phylogenetic, biochemical and chemotaxonomic criteria, two novel genera are proposed, Ileibacterium valens gen. nov., sp. nov. with NYU-BL-A3T (=ATCC TSD-63T=DSM 103668T) as the type strain and Dubosiella newyorkensis gen. nov., sp. nov. with NYU-BL-A4T (=ATCC TSD-64T=DSM 103457T) as the type strain.