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      Functional metagenomic and metabolomics analysis of gut dysbiosis induced by hyperoxia

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          Abstract

          Background

          Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia. Hyperoxia adversely increases the oxygen tension in the gut lumen which harbors the trillions of microorganisms playing an important role in host metabolism and immunity. Nevertheless, the effects of hyperoxia on gut microbiome and metabolome remain unclear, and metagenomic and metabolomics analysis were performed in this mouse study.

          Methods

          C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO 2) of 21% and a hyperoxia (OXY) group exposed to FiO 2 of 80% for 7 days, respectively. Fecal pellets were collected on day 7 and subjected to metagenomic sequencing. Another experiment with the same design was performed to explore the impact of hyperoxia on gut and serum metabolome. Fecal pellets and blood were collected and high-performance liquid chromatography with mass spectrometric analysis was carried out.

          Results

          At the phylum level, hyperoxia increased the ratio of Firmicutes/Bacteroidetes ( p = 0.049). At the species level, hyperoxia reduced the abundance of Muribaculaceae bacterium Isolate-037 ( p = 0.007), Isolate-114 ( p = 0.010), and Isolate-043 ( p = 0.011) etc. Linear discriminant analysis effect size (LEfSe) revealed that Muribaculaceae and Muribaculaceae bacterium Isolate-037, both belonging to Bacteroidetes, were the marker microbes of the CON group, while Firmicutes was the marker microbes of the OXY group. Metagenomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZYmes (CAZy) revealed that hyperoxia provoked disturbances in carbohydrate and lipid metabolism. Fecal metabolomics analysis showed hyperoxia reduced 11-dehydro Thromboxane B2-d4 biosynthesis ( p = 1.10 × 10 −11). Hyperoxia blunted fecal linoleic acid metabolism ( p = 0.008) and alpha-linolenic acid metabolism ( p = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate ( p = 1.58 × 10 −10) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, p = 0.007) and glucagon signaling pathways ( p = 0.007).

          Conclusion

          Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant Muribaculaceae with genomic dysfunction of carbohydrate and lipid metabolism. In addition, hyperoxia suppresses unsaturated fatty acid metabolism in the gut and inhibits the HIF-1 and glucagon signaling pathways in the serum.

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          Most cited references35

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          Structure, Function and Diversity of the Healthy Human Microbiome

          Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.
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            PICRUSt2 for prediction of metagenome functions

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              Sequence and cultivation study of Muribaculaceae reveals novel species, host preference, and functional potential of this yet undescribed family

              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 data annotation. Methods We investigated family S24-7 by combining data from large-scale 16S rRNA gene analysis and from functional and taxonomic studies of metagenomic and cultured species. Results A total of 685 species was inferred by full-length 16S rRNA gene sequence clustering. While many species could not be assigned ecological habitats (93,045 samples analyzed), the mouse was the most commonly identified host (average of 20% relative abundance and nine co-occurring species). Shotgun metagenomics allowed reconstruction of 59 molecular species, of which 34 were representative of the 16S rRNA gene-derived species clusters. In addition, cultivation efforts allowed isolating five strains representing three species, including two novel taxa. Genome analysis revealed that S24-7 spp. are functionally distinct from neighboring families and versatile with respect to complex carbohydrate degradation. Conclusions We provide novel data on the diversity, ecology, and description of bacterial family S24-7, for which the name Muribaculaceae is proposed. Electronic supplementary material The online version of this article (10.1186/s40168-019-0637-2) contains supplementary material, which is available to authorized users.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                28 September 2023
                2023
                : 14
                : 1197970
                Affiliations
                [1] 1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Zunyi Medical University , Zunyi, China
                [2] 2Department of Endocrinology and Metabolism, Affiliated Hospital of Zunyi Medical University , Zunyi, China
                [3] 3Kweichow Moutai Hospital , Renhuai, China
                [4] 4The First Clinical College, Zunyi Medical University , Zunyi, China
                [5] 5Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University , Zunyi, China
                Author notes

                Edited by: Palmiro Poltronieri, National Research Council (CNR), Italy

                Reviewed by: Franca Rossi, Experimental Zooprophylactic Institute of Abruzzo and Molise G. Caporale, Italy; Yan Sun, Masonic Medical Research Institute, United States

                *Correspondence: Tao Chen, 2395086838@ 123456qq.com

                These authors have contributed equally to this work and share first authorship

                Article
                10.3389/fmicb.2023.1197970
                10569423
                37840730
                b9694315-b4ff-4784-b30e-c665efa8a9e9
                Copyright © 2023 Cai, Luo, Dai, Yang, He, Chen, Zhao, Fu, Chen and Xing.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 March 2023
                : 11 September 2023
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 35, Pages: 12, Words: 6481
                Funding
                This study was supported by the National Natural Science Foundation of China (82160370 and 82260167), Science and Technology Program of Guizhou Province (QIANKEHEZHICHEN[2022]YIBAN179, QIANKEHEJICHU[2021]YIBAN441), Science and Technology Planning Project of Guizhou Province (Guizhou department combine basics-ZK[2022] General 639). Zunyi Science and Technology Planning Project [Zun, Shi Kehe HZ word (2022) 279], Kweichow Moutai Hospital (MTyk2022-12, MTyk2022-17) and Educational Department of Guizhou Province [Qianjiaoji 2023(020)].
                Categories
                Microbiology
                Original Research
                Custom metadata
                Microorganisms in Vertebrate Digestive Systems

                Microbiology & Virology
                hyperoxia,metagenomic sequencing,gut microbiome,gut metabolome,gut dysbiosis,serum metabolome,muribaculaceae,linoleic acid metabolism

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