Impacts of PBDE-47 exposure before, during and after pregnancy on the maternal gut microbiome and its association with host metabolism

Abstract Objectives The APOE4 allele is a genetic risk factor for certain diseases, due in part to alterations in lipid and glucose metabolism. The gut microbiota is also known to impact metabolic and can be beneficially modulated by prebiotics. Prebiotics are fermented into metabolites by the gut microbiota. These metabolites act as gut-brain axis components. However, the interaction of the APOE4 allele, gut microbiota, and prebiotics are unknown. The goal of the study was to use prebiotic diet to restore the gut microbiome of mice with human APOE4 (E4FAD) genes. We hypothesized that the microbial compositions of E4 mice fed inulin, compared to control fed, will correlate to metabolites being produced by the microbiome that confer benefit to host metabolism. Methods At 3 months of age the E4FAD mice were fed for 4 months with either control or inulin diet. We used 16S rRNA sequencing to determine gut microbiota diversity and species variations; non-targeted UPLC-MS/MS and GC-MS analysis was used to determine metabolic profiles of blood. Results The inulin fed mice showed a more beneficial microbial taxa profile than those mice that were control fed. Control mice showed higher levels of dimethylglycine, choline, creatine and the polyamine spermine. Higher levels of spermine, specifically, correlate to higher levels of the Proteobacteria which has been implicated in GI disorders. E4 inulin fed mice showed higher levels of bile acids, short chain fatty acids and metabolites involved in energy, increased levels of tryptophan metabolites and robust increases in sphingomyelins. Specifically in E4 inulin fed mice we saw increases in certain genera of bacteria, all of which have been implicated in being beneficial to the composition of the microbiome and producing one or more of the above mentioned metabolites. Conclusions We believe the disparities of microbial metabolite production between E4 inulin fed mice and E4 control fed mice can be attributed to differences in certain taxa that produce these metabolites, and that higher levels of these taxa are due to the dietary intervention of inulin. Despite the APOE4 allele increasing one's risk for certain diseases, we believe that beneficially modulating the gut microbiota may be one way to enhance host metabolism and decrease disease risk over time. Funding Sources NIH/NIDDK T323048107792, NIH/NIA R01AG054459, NIEHS/NIH P42ES007380. Supporting Tables, Images and/or Graphs

Download Full-text

SAT-657 The Gut Microbiome Regulates Host Glucose Homeostasis via Peripheral Serotonin

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.775 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Damien Keating

Keyword(s):

Gut Microbiota ◽

Glucose Homeostasis ◽

Gut Microbiome ◽

Microbiota Composition ◽

Serotonin Synthesis ◽

Pharmacological Inhibition ◽

Genetic Deletion ◽

Underlying Mechanisms ◽

Induced Changes ◽

Host Metabolism

Abstract The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find [1] that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin. [1] The gut microbiome regulates host glucose homeostasis via peripheral serotonin. Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19802-19804. Martin AM, Yabut JM, Choo JM, Page AJ, Sun EW, Jessup CF, Wesselingh SL, Khan WI, Rogers GB, Steinberg GR, Keating DJ.

Download Full-text

Growth Hormone Deficiency and Excess Alter the Gut Microbiome in Adult Male Mice

Endocrinology ◽

10.1210/endocr/bqaa026 ◽

2020 ◽

Vol 161 (4) ◽

Cited By ~ 3

Author(s):

Elizabeth A Jensen ◽

Jonathan A Young ◽

Zachary Jackson ◽

Joshua Busken ◽

Edward O List ◽

...

Keyword(s):

Growth Hormone ◽

Gut Microbiome ◽

Hormone Deficiency ◽

Microbial Profile ◽

Host Growth ◽

Folate Biosynthesis ◽

Host Metabolism ◽

Mouse Lines ◽

Acetate Butyrate

Abstract The gut microbiome has been implicated in host metabolism, endocrinology, and pathophysiology. Furthermore, several studies have shown that gut bacteria impact host growth, partially mediated through the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis. Yet, no study to date has examined the specific role of GH on the gut microbiome. Our study thus characterized the adult gut microbial profile and intestinal phenotype in GH gene-disrupted (GH-/-) mice (a model of GH deficiency) and bovine GH transgenic (bGH) mice (a model of chronic, excess GH action) at 6 months of age. Both the GH-/- and bGH mice had altered microbial signatures, in opposing directions at the phylum and genus levels. For example, GH-/- mice had significantly reduced abundance in the Proteobacteria, Campylobacterota, and Actinobacteria phyla, whereas bGH mice exhibited a trending increase in those phyla compared with respective controls. Analysis of maturity of the microbial community demonstrated that lack of GH results in a significantly more immature microbiome while excess GH increases microbial maturity. Several common bacterial genera were shared, although in opposing directions, between the 2 mouse lines (e.g., decreased in GH-/- mice and increased in bGH mice), suggesting an association with GH. Similarly, metabolic pathways like acetate, butyrate, heme B, and folate biosynthesis were predicted to be impacted by GH. This study is the first to characterize the gut microbiome in mouse lines with altered GH action and indicates that GH may play a role in the growth of certain microbiota thus impacting microbial maturation and metabolic function.

Download Full-text

Modulation of the gut microbiome: a systematic review of the effect of bariatric surgery

Acta Endocrinologica ◽

10.1530/eje-17-0403 ◽

2018 ◽

Vol 178 (1) ◽

pp. 43-56 ◽

Cited By ~ 63

Author(s):

Yan Guo ◽

Zhi-Ping Huang ◽

Chao-Qian Liu ◽

Lin Qi ◽

Yuan Sheng ◽

...

Keyword(s):

Systematic Review ◽

Bariatric Surgery ◽

Gut Microbiota ◽

Strong Evidence ◽

Gut Microbiome ◽

Animal Experiments ◽

Human Metabolism ◽

Microbial Groups ◽

Host Metabolism

Objective Bariatric surgery is recommended for patients with obesity and type 2 diabetes. Recent evidence suggested a strong connection between gut microbiota and bariatric surgery. Design Systematic review. Methods The PubMed and OVID EMBASE were used, and articles concerning bariatric surgery and gut microbiota were screened. The main outcome measures were alterations of gut microbiota after bariatric surgery and correlations between gut microbiota and host metabolism. We applied the system of evidence level to evaluate the alteration of microbiota. Modulation of short-chain fatty acid and gut genetic content was also investigated. Results Totally 12 animal experiments and 9 clinical studies were included. Based on strong evidence, 4 phyla (Bacteroidetes, Fusobacteria, Verrucomicrobia and Proteobacteria) increased after surgery; within the phylum Firmicutes, Lactobacillales and Enterococcus increased; and within the phylum Proteobacteria, Gammaproteobacteria, Enterobacteriales Enterobacteriaceae and several genera and species increased. Decreased microbial groups were Firmicutes, Clostridiales, Clostridiaceae, Blautia and Dorea. However, the change in microbial diversity is still under debate. Faecalibacterium prausnitzii, Lactobacillus and Coprococcus comes are implicated in many of the outcomes, including body composition and glucose homeostasis. Conclusions There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.

Download Full-text

Benefits of fecal microbiota transplantation: A comprehensive review

The Journal of Infection in Developing Countries ◽

10.3855/jidc.12780 ◽

2020 ◽

Vol 14 (10) ◽

pp. 1074-1080

Author(s):

Muluneh Ademe

Keyword(s):

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Short Chain Fatty Acids ◽

Fecal Microbiota ◽

Microbial Colonization ◽

Action Current ◽

Therapeutic Benefits ◽

Wide Range ◽

The One ◽

Host Metabolism

A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflammation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.

Download Full-text

The Time-Dependent Dynamics of Gut Microbiota and the Interaction With Host Metabolism in Mouse Pulmonary Fibrosis Models

10.21203/rs.3.rs-882650/v1 ◽

2021 ◽

Author(s):

Xiao-Hui Yang ◽

Xiu-Juan Jia ◽

Xiao-Sa Chi ◽

Xiao-Meng Wang ◽

Fang-Fang Wang ◽

...

Keyword(s):

Fatty Acids ◽

Pulmonary Fibrosis ◽

Gut Microbiome ◽

Metabolic Changes ◽

Time Dependent ◽

Punicic Acid ◽

Metagenomic Sequencing ◽

Fecal Samples ◽

Serum Metabolites ◽

Host Metabolism

Abstract Background: Pulmonary fibrosis (PF) is a chronic progressive disease whose pathogenesis is thought to be associated with activation of the immune system and consequent metabolic changes. Recent studies suggested that gut microbes are closely related with host's immune response and metabolic changes in fibrotic hosts. However, the dynamic changes of the gut microbiome and the interaction profiles with host metabolism during the development of pulmonary fibrosis remain inconclusive. Results: We collected serum and fecal samples from bleomycin-induced fibrotic mice at 0, 7, 14, and 28 days and performed UPLC-MS analysis on serum metabolites and metagenomic sequencing on fecal samples. It is found that the serum metabolic profile and gut microbiome were significantly altered in mice during the progression of fibrosis. Among the serum metabolites, the levels of three major types of lipids, i.e., glycerolipids, glycerophospholipids, and fatty acids exhibit significant time-dependent changes. The glycerolipid TG and multiple glycerophospholipids (3 PG, 6 PE, and 1 PC) decreased in the early stage of fibrosis and increased in the late stage. The other two types of glycerolipids MG and DG and the fatty acids Cartinine and Punicic acid decreased through the development of fibrosis. In the meantime, we detected significantly elevated abundance of gut microbiome taxa, including Prevotella sp. from Bacteroidetes, Lactobacillus from Firmicutes, and Bifidobacterium from Actinobacteria in mice with pulmonary fibrosis. When compared to the dynamic profiles of serum metabolites, the abundances of gut microbiome show a high level of correlation with that of serum metabolites. The taxa from Bacteroides, such as Butyricimonas_synergistica and Muribaculaceae, show positive correlation with the cluster of glycerophospholipids, while taxa from Firmicutes, such as Clostridioides difficile and Enterococcus faecium exhibit negative correlation. Further functional classification suggested that those taxa are involved in multiple functional modules, such as Transporters, Secretion system, and Metabolism. Conclusions: The results reveal the synergistic changes between the gut microbiome and host metabolism and the dynamic responses of gut microbiome to host fibrosis during the progression of fibrosis.

Download Full-text

Gut Microbiome Variation Modulates the Effects of Dietary Fiber on Host Metabolism

10.21203/rs.3.rs-97357/v1 ◽

2020 ◽

Author(s):

Sofia M Murga-Garrido ◽

Qilin Qilin Hong ◽

Tzu-Wen L Cross ◽

Evan Hutchison ◽

Jessica Han ◽

...

Keyword(s):

Dietary Fiber ◽

Gut Microbiome ◽

Interindividual Variation ◽

Cardiometabolic Health ◽

Metabolic Phenotypes ◽

Microbiome Analysis ◽

Host Genetic ◽

Gnotobiotic Mice ◽

Isocaloric Diets ◽

Host Metabolism

Abstract BackgroundThere is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber.Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host.ResultsWe examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional and metabolomic analyses revealed diet-directed differences between microbiome groups, including variation in amino acids and lipid pathways that were associated with divergent health outcomes.ConclusionThis study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approaches to promote health is unlikely to elicit consistent effects across individuals Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy.

Download Full-text