Bärbel Stecher

Ludwig-Maximilians-University of Munich | LMU · Max-von-Pettenkofer Institute for Hygiene and Medical Microbiology

Background Tremendous amounts of data generated from microbiome research studies during the last decades require not only standards for sampling and preparation of omics data but also clear concepts of how the metadata is prepared to ensure re-use for integrative and interdisciplinary microbiome analysis. Results In this Commentary, we present our...

Microbe-microbe interactions are critical for gut microbiome function. A challenging task to understand health and disease-related microbiome signatures is to move beyond descriptive community-level profiling towards disentangling microbial interaction networks. Here, we aimed to determine members taking on a keystone role in shaping community ecol...

Colorectal cancer is one of the most common cancers and a major cause of mortality. Proinflammatory and antitumor immune responses play critical roles in colitis-associated colon cancer. CCL17, a chemokine of the C-C family and ligand for CCR4, is expressed by intestinal dendritic cells in the steady state and is upregulated during colitis in mouse...

Taurine-respiring gut bacteria produce H 2 S with ambivalent impact on host health. We report the isolation and genomic-ecophysiological characterization of the first taurine-respiring mouse gut bacterium. Taurinivorans muris represents a new widespread species with protective capacity against pathogens and differs from the human gut sulfidogen Bil...

Microbiome research needs comprehensive repositories of cultured bacteria from the intestine of mammalian hosts. We expanded the mouse intestinal bacterial collection (www.dsmz.de/miBC) to 212 strains, all publicly available and taxonomically described. This includes strain-level diversity, small-sized bacteria, and previously undescribed taxa (one...

Gut microbial communities protect the host against a variety of major human gastrointestinal pathogens. Bacteriophages (phages) are ubiquitous in nature and frequently ingested via food and drinking water. Moreover, they are an attractive tool for microbiome engineering due to the lack of known serious adverse effects on the host. However, the func...

The capacity of the intestinal microbiota to degrade otherwise indigestible diet components is known to greatly improve the recovery of energy from food. This has led to the hypothesis that increased digestive efficiency may underlie the contribution of the microbiota to obesity. OligoMM12-colonized gnotobiotic mice have a consistently higher fat m...

The oligo‐mouse‐microbiota (OMM12) is a widely used syncom that colonizes gnotobiotic mice in a stable manner. It provides several fundamental functions to its murine host, including colonization resistance against enteric pathogens. Here, we designed and validated specific fluorescence in situ hybridization (FISH) probes to detect and quantify OMM...

Pyruvate (CH3COCOOH) is the simplest of the alpha-keto acids and is at the interface of several metabolic pathways both in prokaryotes and eukaryotes. In an amino acid-rich environment, fast-growing bacteria excrete pyruvate instead of completely metabolizing it. The role of pyruvate uptake in pathological conditions is still unclear. In this study...

Pyruvate (CH 3 COCOOH) is the simplest of the alpha-keto acids and is at the interface of several metabolic pathways both in prokaryotes and eukaryotes. In an amino acid-rich environment, fast-growing bacteria excrete pyruvate instead of completely metabolizing it. The role of pyruvate uptake in pathological conditions is still unclear. In this stu...

Microbiome research is hampered by the fact that many bacteria are still unknown and by the lack of publicly available isolates. Fundamental and clinical research is in need of comprehensive and well-curated repositories of cultured bacteria from the intestine of mammalian hosts. In this work, we expanded the mouse intestinal bacterial collection (...

A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the...

Understanding the physiological origins of age-related cognitive decline is of critical importance given the rising age of the world’s population1. Previous work in animal models has established a strong link between cognitive performance and the microbiota2,3,4,5, and it is known that the microbiome undergoes profound remodeling in older adults6....

Mus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, here we repo...

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from...

Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2ΔIEC). Hk2ΔIEC mice were le...

Background Akkermansia muciniphila is a member of the human gut microbiota where it resides in the mucus layer and uses mucin as the sole carbon, nitrogen and energy source. A. muciniphila is the only representative of the Verrucomicrobia phylum in the human gut. However, A. muciniphila 16S rRNA gene sequences have also been found in the intestines...

The composition of intrinsic microbial communities determines if invading pathogens will find a suitable niche for colonization and cause infection or be eliminated. Here, we investigate how commensal E. coli mediate colonization resistance (CR) against Salmonella Typhimurium (S. Tm). Using synthetic bacterial communities, we show that the capacity...

Microbiota composition correlates with host metabolic health in both humans and mice. Here we investigated the extent to which a gnotobiotic microbiota can mimic the influence of a complete microbiota on mouse metabolism using an isolator-housed TSE-PhenoMaster® system. We found that energy expenditure was equivalent between germ-free (GF) and spec...

Trillions of bacteria inhabit the mammalian gastrointestinal tract. In the majority of hosts, these symbionts contribute largely to beneficial functions promoting microbe-host homeostasis. However, an increasing number of human diseases is associated with altered microbiota composition and enrichment of certain bacterial species. A well-known examp...

Stx2 is the major virulence factor of EHEC and is associated with an increased risk for HUS in infected patients. The conditions influencing its expression in the intestinal tract are largely unknown. For optimal management and treatment of infected patients, the identification of environmental conditions modulating Stx2 levels in the human gut is...

A key challenge in microbiome research is to predict functionality from microbial community composition. As central microbiota functions are determined by bacterial community networks it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on growth and metabolic interactions of the Oligo-Mou...

Isobiotic mice, with an identical stable microbiota composition, potentially allow models of host-microbial mutualism to be studied over time and between different laboratories. To understand microbiota evolution in these models, we carried out a 6-year experiment in mice colonized with 12 representative taxa. Increased non-synonymous to synonymous...

Gut microbiota and the immune system are in constant exchange shaping both host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40-CD40L axis showed promising results as these molecules are deregulated in certain IBD pati...

With the increased interest in the microbiome research, gnotobiotic animals and techniques emerged again as valuable tools to investigate functional effects of host-microbe and microbe-microbe interactions. The increased demand for gnotobiotic experiments has resulted in the greater need for housing systems for short-term maintenance of gnotobiotic...

Extibacter muris is a newly described mouse gut bacterium which metabolizes cholic acid (CA) to deoxycholic acid (DCA) via 7α-dehydroxylation. Although bile acids influence metabolic and inflammatory responses, few in vivo models exist for studying their metabolism and impact on the host. Mice were colonized from birth with the simplified community...

The role of gut microbiota in colorectal cancer is subject to extensive research. Before usage of biorepositories for microbiome studies, it is crucial to evaluate technical feasibility of microbiome profiling from various biospecimens. The aim of this study was to assess the feasibility of DNA-extraction and microbiome profiling of samples from di...

Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 met...

Although it is generally accepted that dietary fiber is health promoting, the underlying immuno-logical and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was...

Bacteria are excellent model organisms to study mechanisms of social evolution. The production of public goods, e.g., toxin release by cell lysis in clonal bacterial populations, is a frequently studied example of cooperative behavior. Here, we analyze evolutionary stabilization of toxin release by the enteric pathogen Salmonella . The release of c...

The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistence. Coexistence was not dependen...

An increasing number of microorganisms are classified as 'pathobionts' (i.e., organisms that can cause harm under certain circumstances) but there exist no universally used criteria for this definition. In particular, the term is often used for categorizing disease-associated taxa without proof of 'causality'. This creates confusion and distracts f...

Gut microbiota and the immune system are in constant exchange, which shapes both, host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40-CD40L axis showed promising results as these molecules have been described to be de...

The gut microbiome is the largest source of intrinsic non–self-antigens that are continuously sensed by the immune system but typically do not elicit lymphocyte responses. CD4 ⁺ T cells are critical to sustain uninterrupted tolerance to microbial antigens and to prevent intestinal inflammation. However, clinical interventions targeting commensal ba...

Infections with enterohemorrhagic Escherichia coli (EHEC) cause disease ranging from mild diarrhea to hemolytic uremic syndrome (HUS) and are the most common cause of renal failure in children in high income countries. The severity of the disease derives from the release of Shiga toxins (Stx). The use of antibiotics to treat EHEC infections is gene...

The Oligo-Mouse-Microbiota (OMM12) is a recently developed synthetic bacterial community for functional microbiome research in mouse models (Brugiroux et al., 2016). To date, the OMM12 model has been established in several germ-free mouse facilities world-wide and is employed to address a growing variety of research questions related to infection b...

The microbiota confers colonization resistance, which blocks Salmonella gut colonization¹. As diet affects microbiota composition, we studied whether food composition shifts enhance susceptibility to infection. Shifting mice to diets with reduced fibre or elevated fat content for 24 h boosted Salmonella Typhimurium or Escherichia coli gut colonizat...

Tu.ri.ci.mo'nas. L. neut. n. Turicum the Roman name for the city of Zurich; Gr. fem. n. monas a unit, a monad; N.L. fem. n. Turicimonas a unit of Turicum/Zurich; the type strain of the type species was isolated in the Swiss city Zurich. Proteobacteria / Betaproteobacteria / Burkholderiales / Sutterellaceae / Turicimonas Gram stain‐negative, rod sha...

A.cu.ta.li.bac'ter. L. masc. adj. acutalis, tapered, pointed; N.L. masc. n. bacter, rod; N.L. masc. n. Acutalibacter, a rod‐shaped bacterium with tapered ends, pertaining to the cell morphology of the type strain of the type species. Firmicutes / Clostridia / Clostridiales / Ruminococcaceae / Acutalibacter Gram‐stain negative, strictly anaerobic, l...

The intestinal microbiota is a complex ecosystem implicated in host health and disease. Inflammatory bowel disease (IBD) is a multifactorial chronic disorder of the gastrointestinal mucosa. Even though the exact mechanisms are still unknown, the intestinal microbiota is crucial in IBD development. We previously showed that murine norovirus (MNV) in...

Following ingestion, gastrointestinal pathogens compete against the gastrointestinal microbiota and overcome host immune defenses in order to cause infections. Besides employing direct killing mechanisms, the commensal microbiota occupies metabolic niches to outcompete invading pathogens. Salmonella enterica serovar Typhimurium (S. Typhimurium) use...

Objectives Large-scale clinical studies investigating associations between intestinal microbiota signatures and human diseases usually rely on stool samples. However, the timing of repeated stool sample collection cannot be predefined in longitudinal settings. Rectal swabs, being straightforward to obtain, have the potential to overcome this drawba...

Impact of Cary-Blair medium on microbiota profiles. (A): Taxonomic profiles and respective legend at the family level of mock and volunteer samples transported in both Cary-Blair medium and saline solution (NaCl). (B): Beta-diversity calculated as weighted Unifrac and visualized by principal coordinate analysis (PCoA). The mock community is compose...

List of commands used for bioinformatics processing of raw data and microbiome analyses. (TXT)

List of sequenced swab samples and relative information. (XLSX)

Reproducibility and consistency of microbiota profiles. (A): Taxonomic profiles and respective legend at the family level of different technical replicates from swabs and stools of volunteer H1. (B): Beta-diversity calculated as weighted Unifrac and visualized by principal coordinate analysis (PCoA). (PDF)

Fasta control sequences. (FNA)

Characteristics of the samples used for pipeline validation. (XLSX)

Dual-indexed PCR amplification primer sequences. Red: Illumina adapter sequence. Black: variability region. Green: specific sample barcode. Blue: forward primer targeting the specific 16S rRNA regions V3-V4. Purple: reverse primer targeting the specific 16S rRNA region V3-V4. (XLSX)

Information and taxonomy classification of the control samples. (XLSX)

The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut. Unexpectedly, in contrast to mucus-proficient littermates, genetically deficient...

Background Bacteria within family S24-7 (phylum Bacteroidetes) are dominant in the mouse gut microbiota and detected in the intestine of other animals. Because they had not been cultured until recently and the family classification is still ambiguous, interaction with their host was difficult to study and confusion still exists regarding sequence d...

Escherichia coli Mt1B1, a mouse isolate, is a facultative anaerobic bacterium which was shown to counteract Salmonella enterica serovar Typhimurium infection in a mouse model. In the present study, we describe the complete genome sequence of E. coli Mt1B1, composed of a 5.1-Mb chromosome and a 62.6-kb plasmid.

Gene expression levels in clonal bacterial groups have been found to be spatially correlated. These correlations can partly be explained by the shared lineage history of nearby cells, although they could also arise from local cell-cell interactions. Here, we present a quantitative framework that allows us to disentangle the contributions of lineage...

Infection by Salmonella enterica serovar Typhimurium is accompanied by dysbiosis and a decrease of microbiota-derived butyrate. In this issue of Cell Host & Microbe, Gillis et al. (2018) demonstrate that the lack of butyrate reprograms colonic epithelial metabolism toward lactate fermentation. Lactate is then used as a respiratory electron donor, s...

The Oligo-Mouse-Microbiota (Oligo-MM ¹² ) is a community of 12 mouse intestinal bacteria to be used for microbiome research in gnotobiotic mice. We present here the high-quality whole genome sequences of the Oligo-MM ¹² strains, which were obtained by combining the accuracy of the Illumina platforms with the long reads of the PacBio technology.

The mammalian gut microbiota is dominated by populations of bacteria, mostly strict anaerobes. Because these bacteria can influence the health of their host, it is important to investigate their diversity and functions, which can be done via culture-based or molecular approaches. In recent years, microbiologists have very often preferred the use of...

Metagenomics revolutionized the field of microbial ecology, giving access to Gb-sized datasets of microbial communities under natural conditions. This enables fine-grained analyses of the functions of community members, studies of their association with phenotypes and environments, as well as of their microevolution and adaptation to changing envir...

Nature Communications 8 : Article number: 14715 10.1038/ncomms14715 ( 2017 ); Published: 9 March 2017 ; Updated: 24 April 2017 In Fig. 2 of this Article, the inset image in the bottom panel was inadvertently omitted during the production process.

Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+ dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+ (RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microb...

Supplementary Figures 1-7 and Supplementary Methods

Experimental reproducibility between laboratories is a major translational obstacle worldwide, particularly in studies investigating immunomodulatory therapies in relation to brain disease. In recent years increasing attention has been drawn towards the gut microbiota as a key factor in immune cell polarization. Moreover, manipulation of the gut mi...

Mucispirillum schaedleri is an abundant inhabitant of the intestinal mucus layer of rodents and other animals and has been suggested to be a pathobiont, a commensal that plays a role in disease. In order to gain insights into its lifestyle, we analyzed the genome and transcriptome of M. schaedleri ASF 457 and performed physiological experiments to...

Bile acids, important mediators of lipid absorption, also act as hormone-like regulators and as antimicrobial molecules. In all these functions their potency is modulated by a variety of chemical modifications catalyzed by bacteria of the healthy gut microbiota, generating a complex variety of secondary bile acids. Intestinal commensal organisms ar...