A combinatory approach using metabolomics and gut microbiome analysis techniques was performed to unravel the nature and specificity of metabolic profiles related to gut ecology in obesity. This study focused on gut and liver metabolomics of two different mouse strains, the C57BL/6J (C57J) and the C57BL/6N (C57N) fed with high-fat diet (HFD) for 3 weeks, causing dietinduced obesity in C57N, but not in C57J mice. Furthermore, a 16S-ribosomal RNA comparative sequence analysis using 454 pyrosequencing detected significant differences between the microbiome of the two strains on phylum level for Firmicutes, Deferribacteres and Proteobacteria that propose an essential role of the microbiome in obesity susceptibility. Gut microbial and liver metabolomics were followed by a combinatory approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ultra performance liquid chromatography time of tlight MS/MS with subsequent multivariate statistical analysis, revealing distinctive host and microbial metabolome patterns between the C57J and the C57N strain. Many taurine-conjugated bile acids (TBAs) were significantly elevated in the cecum and decreased in liver samples from the C57J phenotype likely displaying different energy utilization behavior by the bacterial community and the host. Furthermore, several metabolite groups could specifically be associated with the C57N phenotype involving fatty acids, eicosanoids and urobilinoids. The mass differences based metabolite network approach enabled to extend the range of known metabolites to important bile acids (BAs) and novel taurine conjugates specific for both strains. In summary, our study showed clear alterations of the metabolome in the gastrointestinal tract and liver within a HFD-induced obesity mouse model in relation to the host-microbial nutritional adaptation.

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The gut microbiota generates a huge pool of unknown metabolites, and their identification and characterization is a key challenge in metabolomics. However, there are still gaps on the studies of gut microbiota and their chemical structures. In this investigation, an unusual class of bacterial sulfonolipids (SLs) is detected in mouse cecum, which was originally found in environmental microbes. We have performed a detailed molecular level characterization of this class of lipids by combining high-resolution mass spectrometry and liquid chromatography analysis. Eighteen SLs that differ in their capnoid and fatty acid chain compositions were identified. The SL called “sulfobacin B” was isolated, characterized, and was significantly increased in mice fed with high-fat diets. To reveal bacterial producers of SLs, metagenome analysis was acquired and only two bacterial genera, i.e., Alistipes and Odoribacter, were revealed to be responsible for their production. This knowledge enables explaining a part of the molecular complexity introduced by microbes to the mammalian gastrointestinal tract and can be used as chemotaxonomic evidence in gut microbiota.

In our mouse model, gastric acid-suppression is associated with antigen-specific IgE and anaphylaxis development. We repeatedly observed non-responder animals protected from food allergy. Here, we aimed to analyse reasons for this protection. Ten out of 64 mice, subjected to oral ovalbumin (OVA) immunizations under gastric acid-suppression, were non-responders without OVA-specific IgE or IgG1 elevation, indicating protection from allergy. In these non-responders, allergen challenges confirmed reduced antigen uptake and lack of anaphylactic symptoms, while in allergic mice high levels of mouse mast-cell protease-1 and a body temperature reduction, indicative for anaphylaxis, were determined. Upon OVA stimulation, significantly lower IL-4, IL-5, IL-10 and IL-13 levels were detected in non-responders, while IL-22 was significantly higher. Comparison of fecal microbiota revealed differences of bacterial communities on single bacterial Operational-Taxonomic-Unit level between the groups, indicating protection from food allergy being associated with a distinct microbiota composition in a non-responding phenotype in this mouse model.

Permeable sediments and associated microbial communities play a fundamental role in nutrient recycling within coral reef ecosystems by ensuring high levels of primary production in oligotrophic environments. A previous study on organic matter degradation within biogenic carbonate and terrigenous silicate reef sands in the Red Sea suggested that observed sand-specific differences in microbial activity could be caused by variations in microbial biomass and diversity. Here, we tested this hypothesis by comparing bacterial abundance and community structure in both sand types, and by further exploring the structuring effects of time (season) and space (sediment depth, in/out-reef). Changes in bacterial community structure, as determined via automated ribosomal intergenic spacer analysis (ARISA), were primarily driven by sand mineralogy at specific seasons, sediment depths and reef locations. By coupling ARISA with 16S-ITS rRNA sequencing, we detected significant community shifts already at the bacterial class level, with Proteobacteria (Gamma-, Delta-, Alpha-) and Actinobacteria being prominent members of the highly diverse communities. Overall, our findings suggest that reef sand-associated bacterial communities vary substantially with sand type. Especially in synergy with environmental variation over time and space, mineralogical differences seem to play a central role in maintaining high levels of bacterial community heterogeneity. The local co-occurrence of carbonate and silicate sands may thus significantly increase the availability of microbial niches within a single coral reef ecosystem.

A metabolic disorder such as Type-2 Diabetes mellitus (T2DM) is a complex disease induced by genetic, environmental, and nutritional factors. The db/db mouse model, bearing a nonfunctional leptin receptor, is widely used to investigate the pathophysiology of T2DM. Fecal extracts of db/db and wild-type littermates were studied to unravel a broad spectrum of new and relevant metabolites related to T2DM as proxies of the interplay of gut microbiome and murine metabolomes. The nontargeted metabolomics approach consists of an integrated analytical concept of high-resolution mass spectrometry FT-ICR-MS, followed by UPLC-TOF-MS/MS experiments. We demonstrate that a metabolic disorder such as T2DM affects the gastrointestinal tract environment, thereby influencing different metabolic pathways and their respective metabolites in diabetic mice. Fatty acids, bile acids concerning cholic and deoxycholic acid, and steroid metabolism were highly discriminative comparing fecal meta-metabolomes of wt and db/db mice. Furthermore, sulfur-(S)-containing metabolites including N-acyl taurines were altered in diabetic mice, enabling us to focus on S-containing metabolites, especially the sulfate and taurine conjugates of bile and fatty acids. Different sulfate containing bile acids including sulfocholic acid, oxocholic acid sulfate, taurocholic acid sulfate, and cyprinol sulfate were significantly altered in diabetic mice. Moreover, we identified 12 new sulfate and taurine conjugates of hydroxylated fatty acids with significant importance in T2DM metabolism in db/db mice.

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