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Molecular networking-based lipid profiling and multi-omics approaches reveal new contributions of functional vanilloids to gut microbiota and lipometabolism changes.

ABSTRACT: Obesity is now recognized as an epidemic, requiring rapid intervention. We previously demonstrated that vanilloids from the African spice known as Grains of Paradise (GOP) exhibit strong anti-obesity effects. Here, the molecular mechanism behind the obesity prevention property of the GOP extract was investigated by employing molecular networking-based lipid profiling and 16S rRNA sequencing. Administration of either GOP extract or two of its components, 6-paradol and 6-gingerol, reversed the unbalanced gut microbiota composition induced by a high-fat diet (HFD) with a decrease in Firmicutes / Bacteroidetes ratio and increase in genera Bifidobacterium and Akkermansia. Moreover, GOP extract ameliorated abnormal fatty acid metabolism in gut bacteria. Furthermore, lipid molecular networking revealed differences in lipid composition, such as triglycerides and bile acids, in the feces. These results suggest that 6-paradol and 6-gingerol can restore an unhealthy gut environment and prevent lipid absorption, a possible consequence of the reconstruction of the gut microbiota.

SUBMITTER: Hattori H

PROVIDER: S-EPMC9309231 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Molecular networking-based lipid profiling and multi-omics approaches reveal new contributions of functional vanilloids to gut microbiota and lipometabolism changes.

Hattori Hiroyuki H Moriyama Akihiro A Ohno Tomoki T Shibata Takahiro T Iwahashi Hitoshi H Mitsunaga Tohru T

Food chemistry. Molecular sciences 20220718

Obesity is now recognized as an epidemic, requiring rapid intervention. We previously demonstrated that vanilloids from the African spice known as Grains of Paradise (GOP) exhibit strong anti-obesity effects. Here, the molecular mechanism behind the obesity prevention property of the GOP extract was investigated by employing molecular networking-based lipid profiling and 16S rRNA sequencing. Administration of either GOP extract or two of its components, 6-paradol and 6-gingerol, reversed the unb ...[more]

PMID: 35898333

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Project description:Gut microbiota and related metabolites are both crucial factors that significantly influence how individuals with Crohn's disease respond to immunotherapy. However, little is known about the interplay among gut microbiota, metabolites, Crohn's disease, and the response to anti-α4β7-integrin in current studies. Our research utilized 2,4,6-trinitrobenzene sulfonic acid to induce colitis based on the humanized immune system mouse model and employed a combination of whole-genome shotgun metagenomics and non-targeted metabolomics to investigate immunotherapy responses. Additionally, clinical cases with Crohn's disease initiating anti-α4β7-integrin therapy were evaluated comprehensively. Particularly, 16S-rDNA gene high-throughput sequencing and targeted bile acid metabolomics were conducted at weeks 0, 14, and 54. We found that anti-α4β7-integrin therapy has shown significant potential for mitigating disease phenotypes in remission-achieving colitis mice. Microbial profiles demonstrated that not only microbial composition but also microbially encoded metabolic pathways could predict immunotherapy responses. Metabonomic signatures revealed that bile acid metabolism alteration, especially elevated secondary bile acids, was a determinant of immunotherapy responses. Especially, the remission mice significantly enriched the proportion of the beneficial Lactobacillus and Clostridium genera, which were correlated with increased gastrointestinal levels of BAs involving lithocholic acid and deoxycholic acid. Moreover, most of the omics features observed in colitis mice were replicated in clinical cases. Notably, anti-α4β7 integrin provided sustained therapeutic benefits in clinical remitters during follow-up, and long-lasting remission was linked to persistent changes in the microbial-related bile acids. In conclusion, gut microbiota-mediated bile acid metabolism alteration could play a crucial role in regulating immunotherapy responses to anti-α4β7-integrin in Crohn's disease. Therefore, the identification of prognostic microbial signals facilitates the advancement of targeted probiotics that activate anti-inflammatory bile acid metabolic pathways, thereby improving immunotherapy responses. The integrated multi-omics established in our research provide valuable insights into potential mechanisms that impact treatment responses in complex diseases.

Project description:BackgroundSchizophrenia is a persistent incurable mental disorder and is characterized by the manifestation of negative emotions and behaviors with anxiety and depression, fear and insecurity, self-harm and social withdrawal. The intricate molecular mechanisms underlying this phenomenon remain largely elusive. Accumulating evidence points towards the gut microbiota exerting an influence on brain function via the gut-brain axis, potentially contributing to the development of schizophrenia. Therefore, the objective of this study is to delineate the gut microbial composition and metabolic profile of fecal samples from individuals with schizophrenia.MethodsLiquid chromatography-mass spectrometry (LC-MS) and 16S ribosomal RNA (16S rRNA) gene sequencing were employed to analyze fecal metabolites and gut microbiota profiles in a cohort of 29 patients diagnosed with schizophrenia and 30 normal controls. The microbial composition of fecal samples was determined through the 16S rRNA gene sequencing, and microbial α-diversity and β-diversity indices were calculated. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed to analyze the distribution of samples. The metabolites and gut microbiota exhibiting differential expression were identified through the application of biological variance criteria. Co-occurrence analysis of bacteria and metabolites was conducted using the spearman's rank correlation coefficient and visualized in a circular layout with the Cytoscape software.ResultsThe findings of the study indicated a lack of substantial evidence supporting significant disparities in α-diversity and β-diversity between individuals with schizophrenia and normal controls. In terms of metabolomics, a discernible pattern in sample distribution between the two groups was observed. Our analysis has revealed 30 bacterial species and 45 fecal metabolites that exhibited notable differences in abundance between individuals diagnosed with schizophrenia and normal controls. These alterations in multilevel omics have led to the development of a co-expression network associated with schizophrenia. The perturbed microbial genes and fecal metabolites consistently demonstrated associations with amino acid and lipid metabolism, which play essential roles in regulating the central nervous system.ConclusionOur results offered profound insights into the impact of imbalanced gut microbiota and metabolism on brain function in individuals with schizophrenia.

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Molecular networking-based lipid profiling and multi-omics approaches reveal new contributions of functional vanilloids to gut microbiota and lipometabolism changes.

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Molecular networking-based lipid profiling and multi-omics approaches reveal new contributions of functional vanilloids to gut microbiota and lipometabolism changes.

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