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Dilmore AH, Kuplicki R, McDonald D, Kumar M, Estaki M, Youngblut N, Tyakht A, Ackermann G, Blach C, MahmoudianDehkordi S, Dunlop BW, Bhattacharyya S, Guinjoan S, Mandaviya P, Ley RE, Kaddaruh-Dauok R, Paulus MP, Knight R. Medication use is associated with distinct microbial features in anxiety and depression. Mol Psychiatry 2025; 30:2545-2557. [PMID: 39794490 DOI: 10.1038/s41380-024-02857-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 11/11/2024] [Accepted: 11/22/2024] [Indexed: 01/13/2025]
Abstract
This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing (16S) and shallow shotgun sequencing (WGS) were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and Neurocomputational Mechanisms of Affiliation and Personality Study Center for Biomedical Research Excellence (NeuroMAP CoBRE) cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. Though the effect sizes were larger in females than males, similar trends emerged for both sexes. These findings encourage future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments.
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Affiliation(s)
- Amanda Hazel Dilmore
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA
| | | | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Megha Kumar
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Mehrbod Estaki
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Nicholas Youngblut
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Alexander Tyakht
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Gail Ackermann
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | - Colette Blach
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
- Duke Institute of Brain Sciences, Duke University, Durham, NC, USA
| | | | - Boadie W Dunlop
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Sudeepa Bhattacharyya
- Department of Biological Sciences, Arkansas Biosciences Institute, Arkansas State University, Jonesboro, AR, USA
| | | | - Pooja Mandaviya
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Ruth E Ley
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Rima Kaddaruh-Dauok
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
- Department of Medicine, Duke University, Durham, NC, USA
- Duke Institute of Brain Sciences, Duke University, Durham, NC, USA
| | | | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
- Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA.
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
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Nie HY, Zhao MF, Wu TY, Zou MJ, Tang YP, Wang XC, Wang NN, Zhou ZY, Bi Y, Zhao Y, Sun XT, Zhang JZ, Fang L, Li CJ. Elevated mevalonolactone from Ruminococcus torques contributes to Metabolically Abnormal Obesity development. J Biol Chem 2025:110281. [PMID: 40412522 DOI: 10.1016/j.jbc.2025.110281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 04/03/2025] [Accepted: 04/14/2025] [Indexed: 05/27/2025] Open
Abstract
Obese individuals are categorized as either "Metabolically Abnormal Obesity" (MAO) or "Metabolically Healthy Obesity" (MHO) based on their insulin resistance and metabolic disorders. However, the intrinsic mechanism remains largely unknown. Through examining gut microbiota and fecal metabolome of MAO and MHO patients, we identified intestinal microorganism Ruminococcus torques (R. torques) and its metabolite mevalonolactone (MVL) as risk factors for insulin resistance and metabolic disorders. Both R. torques and MVL administration results in MAO phenotype in mice. In general, MVL is an intermediate metabolite in the eukaryotic mevalonate (MVA) pathway, however we found that prokaryote R. torques, has the potential to produce MVL. We further showed that MVL could directly bind to the transcription factor ZNF384, triggering its nucleation and subsequent binding to the promoter regions of Ggps1. Ggps1 enhance Ras prenylation and promotes insulin resistance. In conclusion, the abnormal colonization of R. torques in gut leads to an increased level of MVL in patients. This, in turn, affects the expression of Ggps1 via ZNF384, ultimately contributing to the development of MAO.
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Affiliation(s)
- Hong-Yu Nie
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Meng-Fei Zhao
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Tian-Yu Wu
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China
| | - Ming-Jie Zou
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Yi-Ping Tang
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Xiao-Chen Wang
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Nan-Nan Wang
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Zi-Yue Zhou
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Yan Bi
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Yue Zhao
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
| | - Xi-Tai Sun
- Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China
| | - Jing-Zi Zhang
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China.
| | - Lei Fang
- Model Animal Research Center of Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China.
| | - Chao-Jun Li
- State Key Laboratory of Reproductive Medicine and Offspring Heath, Nanjing Medical University, Nanjing 211166, China.
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Lee SK, Kwon JH, Jang JW, Bae SH, Yoon SK, Jung ES, Choi JY. The Critical Role of Regulatory T Cells in Immune Tolerance and Rejection Following Liver Transplantation: Interactions With the Gut Microbiome. Transplantation 2025; 109:784-793. [PMID: 39375899 DOI: 10.1097/tp.0000000000005220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Abstract
Liver transplantation (LT) is the ultimate treatment for patients with end-stage liver disease or early hepatocellular carcinoma. In the context of LT, because of the unique immunological characteristics of human liver allograft, 5%-20% of selected LT recipients can achieve operational tolerance. Nonetheless, there remains a risk of rejection in LT patients. Maintaining immune homeostasis is thus crucial for improving clinical outcomes in these patients. In mechanism, several immune cells, including dendritic cells, Kupffer cells, myeloid-derived suppressor cells, hepatic stellate cells, regulatory B cells, and CD4 + regulatory T cells (Treg), contribute to achieving tolerance following LT. In terms of Treg, it plays a role in successfully minimizing immunosuppression or achieving tolerance post-LT while also reducing the risk of rejection. Furthermore, the gut microbiome modulates systemic immune functions along the gut-liver axis. Recent studies have explored changes in the microbiome and its metabolites under various conditions, including post-LT, acute rejection, and tolerance. Certain functional microbiomes and metabolites exhibit immunomodulatory functions, such as the augmentation of Treg, influencing immune homeostasis. Therefore, understanding the mechanisms of tolerance in LT, the role of Treg in tolerance and rejection, as well as their interactions with gut microbiome, is vital for the management of LT patients.
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Affiliation(s)
- Soon Kyu Lee
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jung Hyun Kwon
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jeong Won Jang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Si Hyun Bae
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Eun Sun Jung
- Department of Pathology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Yamamura R, Okubo R, Ukawa S, Nakamura K, Okada E, Nakagawa T, Imae A, Kimura T, Tamakoshi A. Increased fecal glycocholic acid levels correlate with obesity in conjunction with the depletion of archaea: The Dosanco Health Study. J Nutr Biochem 2025; 139:109846. [PMID: 39863085 DOI: 10.1016/j.jnutbio.2025.109846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 12/30/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
Recent studies have focused on the relationship between obesity and gut microbiota. This study aims to identify fecal components and gut bacterial species associated with different BMI categories. In this study, 538 participants aged ≥18 years were categorized into underweight, normal, and obese groups based on BMI (cutoffs: 18.5 and 25.0 kg/m²). We compared 30 fecal components among these groups and calculated correlation coefficients between each component and BMI. Participants were then divided into quartiles based on fecal component levels correlated with BMI, and the prevalence ratio (PR) of obesity was calculated, adjusted for confounding factors. We also analyzed the composition and diversity of gut microbiota and bacterial gene expression among the quartiles for each fecal component. Fecal glycocholic acid (GCA) showed a significant positive correlation with BMI. The PR for obesity in the highest quartile of fecal GCA was 3.30 (95% CI, 1.21-9.54), indicating a significantly higher risk of obesity compared to the lowest quartile. Gut microbiota analysis revealed significant differences in the abundance of Ruminococcaceae Incertae Sedis, Faecalibacterium, and Methanobrevibacter, with Methanobrevibacter being absent in the higher quartiles of fecal GCA. Additionally, gene expression for enzymes involved in the deconjugation of conjugated bile acids, including GCA, was downregulated in the highest quartile. Increased fecal GCA levels are positively correlated with obesity, alongside a depletion of archaea.
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Affiliation(s)
- Ryodai Yamamura
- Division of Biomedical Oncology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
| | - Ryo Okubo
- Department of Neuropsychiatry, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
| | - Shigekazu Ukawa
- Osaka Metropolitan University Graduate School of Human Life and Ecology, Sumiyoshi, Osaka, Japan; Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Koshi Nakamura
- Department of Public Health and Epidemiology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan; Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Emiko Okada
- The Health Care Science Institute, Minato-ku, Tokyo, Japan; Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | | | - Akihiro Imae
- The Hokkaido Centre for Family Medicine, Sapporo, Japan
| | - Takashi Kimura
- Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan
| | - Akiko Tamakoshi
- Department of Public Health, Faculty of Medicine, Hokkaido University, Sapporo, Japan
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Lin X, Xia L, Zhou Y, Xie J, Tuo Q, Lin L, Liao D. Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5. Int J Mol Sci 2025; 26:4240. [PMID: 40362481 PMCID: PMC12072030 DOI: 10.3390/ijms26094240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2025] [Revised: 04/22/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
Bile acids and their corresponding intestinal epithelial receptors, the farnesoid X receptor (FXR), the G protein-coupled bile acid receptor (TGR5), play crucial roles in the physiological and pathological processes of intestinal epithelial cells. These acids and receptors are involved in the regulation of intestinal absorption, signal transduction, cellular proliferation and repair, cellular senescence, energy metabolism, and the modulation of gut microbiota. A comprehensive literature search was conducted using PubMed, employing keywords such as bile acid, bile acid receptor, FXR (nr1h4), TGR5 (gpbar1), intestinal epithelial cells, proliferation, differentiation, senescence, energy metabolism, gut microbiota, inflammatory bowel disease (IBD), colorectal cancer (CRC), and irritable bowel syndrome (IBS), with a focus on publications available in English. This review examines the diverse effects of bile acid signaling and bile receptor pathways on the proliferation, differentiation, senescence, and energy metabolism of intestinal epithelial cells. Additionally, it explores the interactions between bile acids, their receptors, and the microbiota, as well as the implications of these interactions for host health, particularly in relation to prevalent intestinal diseases. Finally, the review highlights the importance of developing highly specific ligands for FXR and TGR5 receptors in the context of metabolic and intestinal disorders.
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Affiliation(s)
| | | | | | | | | | | | - Duanfang Liao
- Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China; (X.L.); (L.X.); (Y.Z.); (J.X.); (Q.T.); (L.L.)
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6
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Fu L, Baranova A, Cao H, Zhang F. Gut microbiome links obesity to type 2 diabetes: insights from Mendelian randomization. BMC Microbiol 2025; 25:253. [PMID: 40289103 PMCID: PMC12034155 DOI: 10.1186/s12866-025-03968-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 04/15/2025] [Indexed: 04/30/2025] Open
Abstract
BACKGROUND Research has established links between the gut microbiome (GM) and both obesity and type 2 diabetes (T2D), which is much discussed, but underexplored. This study employed body mass index (BMI) as the measurement of obesity to delve deeper into the correlations from a genetic perspective. METHODS We performed the Mendelian randomization (MR) analysis to examine the causal effects of GM on T2D and BMI, and vice versa. Genome-wide association study (GWAS) summary datasets were utilized for the analysis, including T2D (N = 933,970), BMI (N = 806,834), and two GM datasets from the international consortium MiBioGen (211 taxa, N = 18,340) and the Dutch Microbiome Project (DMP) (207 taxa, N = 7,738). These datasets mainly cover European populations, with additional cohorts from Asia and other regions. To further explore the potential mediating role of GM in the connections between BMI and T2D, their interaction patterns were summarized into a network. RESULTS MR analysis identified 9 taxa that showed protective properties against T2D. Seven species were within the Firmicutes and Bacteroidales phyla in the DMP, and two were from the MiBioGen (Odds Ratio (OR): 0.94-0.95). Conversely, genetic components contributing to the abundance of 12 taxa were associated with increased risks of T2D (OR: 1.04-1.12). Furthermore, T2D may elevate the abundance of seven taxa (OR: 1.03-1.08) and reduce the abundance of six taxa (OR: 0.93-0.97). In the analysis of the influence of the genetic component of BMI on GM composition, BMI affected 52 bacterial taxa, with 28 decreasing (OR: 0.75-0.92) and 24 increasing (OR: 1.08-1.27). Besides, abundances of 25 taxa were negatively correlated with BMI (OR: 0.95-0.99), while positive correlations were detected for 14 taxa (OR: 1.01-1.05). Notably, we uncovered 11 taxa genetically associated with both BMI and T2D, which formed an interactive network. CONCLUSIONS Our findings provide evidence for the GM-mediated links between obesity and T2D. The identification of relevant GM taxa offers valuable insights into the potential role of the microbiome in these diseases.
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Affiliation(s)
- Li Fu
- Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China
| | - Ancha Baranova
- School of Systems Biology, George Mason University, Manassas, VA, 20110, USA
- Research Centre for Medical Genetics, Moscow, 115478, Russia
| | - Hongbao Cao
- School of Systems Biology, George Mason University, Manassas, VA, 20110, USA
| | - Fuquan Zhang
- Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
- Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
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Mercurio G, Giacco A, Scopigno N, Vigliotti M, Goglia F, Cioffi F, Silvestri E. Mitochondria at the Crossroads: Linking the Mediterranean Diet to Metabolic Health and Non-Pharmacological Approaches to NAFLD. Nutrients 2025; 17:1214. [PMID: 40218971 PMCID: PMC11990101 DOI: 10.3390/nu17071214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2025] [Revised: 03/18/2025] [Accepted: 03/28/2025] [Indexed: 04/14/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern that is closely linked to metabolic syndrome, yet no approved pharmacological treatment exists. The Mediterranean diet (MD) emerged as a first-line dietary intervention for NAFLD, offering metabolic and hepatoprotective benefits. Now conceptualized as a complex chemical matrix rich in bioactive compounds, the MD exerts antioxidant and anti-inflammatory effects, improving insulin sensitivity and lipid metabolism. Mitochondria play a central role in NAFLD pathophysiology, influencing energy metabolism, oxidative stress, and lipid homeostasis. Emerging evidence suggests that the MD's bioactive compounds enhance mitochondrial function by modulating oxidative phosphorylation, biogenesis, and mitophagy. However, most research has focused on individual compounds rather than the MD as a whole, leaving gaps in understanding its collective impact as a complex dietary pattern. This narrative review explores how the MD and its bioactive compounds influence mitochondrial health in NAFLD, highlighting key pathways such as mitochondrial substrate control, dynamics, and energy efficiency. A literature search was conducted to identify relevant studies on the MD, mitochondria, and NAFLD. While the search was promising, our understanding remains incomplete, particularly when current knowledge is limited by the lack of mechanistic and comprehensive studies on the MD's holistic impact. Future research integrating cutting-edge experimental approaches is needed to elucidate the intricate diet-mitochondria interactions. A deeper understanding of how the MD influences mitochondrial health in NAFLD is essential for developing precision-targeted nutritional strategies that can effectively prevent and manage the disease.
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Affiliation(s)
| | | | | | | | | | | | - Elena Silvestri
- Department of Science and Technology, University of Sannio, Via De Sanctis, 82100 Benevento, Italy; (G.M.); (A.G.); (N.S.); (M.V.); (F.G.); (F.C.)
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Lan F, Wang X, Zhou Q, Li X, Jin J, Zhang W, Wen C, Wu G, Li G, Yan Y, Yang N, Sun C. Deciphering the coordinated roles of the host genome, duodenal mucosal genes, and microbiota in regulating complex traits in chickens. MICROBIOME 2025; 13:62. [PMID: 40025569 PMCID: PMC11871680 DOI: 10.1186/s40168-025-02054-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 02/01/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND The complex interactions between host genetics and the gut microbiome are well documented. However, the specific impacts of gene expression patterns and microbial composition on each other remain to be further explored. RESULTS Here, we investigated this complex interplay in a sizable population of 705 hens, employing integrative analyses to examine the relationships among the host genome, mucosal gene expression, and gut microbiota. Specific microbial taxa, such as the cecal family Christensenellaceae, which showed a heritability of 0.365, were strongly correlated with host genomic variants. We proposed a novel concept of regulatability ( r b 2 ), which was derived from h2, to quantify the cumulative effects of gene expression on the given phenotypes. The duodenal mucosal transcriptome emerged as a potent influencer of duodenal microbial taxa, with much higher r b 2 values (0.17 ± 0.01, mean ± SE) than h2 values (0.02 ± 0.00). A comparative analysis of chickens and humans revealed similar average microbiability values of genes (0.18 vs. 0.20) and significant differences in average r b 2 values of microbes (0.17 vs. 0.04). Besides, cis ( h cis 2 ) and trans heritability ( h trans 2 ) were estimated to assess the effects of genetic variations inside and outside the cis window of the gene on its expression. Higher h trans 2 values than h cis 2 values and a greater prevalence of trans-regulated genes than cis-regulated genes underscored the significant role of loci outside the cis window in shaping gene expression levels. Furthermore, our exploration of the regulatory effects of duodenal mucosal genes and the microbiota on 18 complex traits enhanced our understanding of the regulatory mechanisms, in which the CHST14 gene and its regulatory relationships with Lactobacillus salivarius jointly facilitated the deposition of abdominal fat by modulating the concentration of bile salt hydrolase, and further triglycerides, total cholesterol, and free fatty acids absorption and metabolism. CONCLUSIONS Our findings highlighted a novel concept of r b 2 to quantify the phenotypic variance attributed to gene expression and emphasize the superior role of intestinal mucosal gene expressions over host genomic variations in elucidating host‒microbe interactions for complex traits. This understanding could assist in devising strategies to modulate host-microbe interactions, ultimately improving economic traits in chickens.
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Affiliation(s)
- Fangren Lan
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Xiqiong Wang
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Qianqian Zhou
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Xiaochang Li
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Jiaming Jin
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Wenxin Zhang
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Chaoliang Wen
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Guiqin Wu
- Beijing Engineering Research Centre of Layer, Beijing, 101206, China
| | - Guangqi Li
- Beijing Engineering Research Centre of Layer, Beijing, 101206, China
| | - Yiyuan Yan
- Beijing Engineering Research Centre of Layer, Beijing, 101206, China
| | - Ning Yang
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China.
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China.
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
| | - Congjiao Sun
- State Key Laboratory of Animal Biotech Breeding and Frontier Science Center of Molecular Design Breeding, China Agricultural University, Beijing, 100193, China.
- National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, China Agricultural University, Beijing, 100193, China.
- Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
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Pattaroni C, Marsland BJ, Harris NL. Early-Life Host-Microbial Interactions and Asthma Development: A Lifelong Impact? Immunol Rev 2025; 330:e70019. [PMID: 40099971 PMCID: PMC11917194 DOI: 10.1111/imr.70019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 02/19/2025] [Accepted: 02/28/2025] [Indexed: 03/20/2025]
Abstract
Childhood is a multifactorial disease, and recent research highlights the influence of early-life microbial communities in shaping disease risk. This review explores the roles of the gut and respiratory microbiota in asthma development, emphasizing the importance of early microbial exposure. The gut microbiota has been particularly well studied, with certain taxa like Faecalibacterium and Bifidobacterium linked to asthma protection, whereas short-chain fatty acids produced by gut microbes support immune tolerance through the gut-lung axis. In contrast, the respiratory microbiota, though low in biomass, shows consistent associations between early bacterial colonization by Streptococcus, Moraxella, and Haemophilus and increased asthma risk. The review also addresses the emerging roles of the skin microbiota and environmental fungi in asthma, though findings remain inconsistent. Timing is a critical factor, with early-life disruptions, such as antibiotic use, potentially leading to increased asthma risk. Despite significant advances, there are still unresolved questions about the long-term consequences of early microbial perturbations, particularly regarding whether microbial dysbiosis is a cause or consequence of asthma. This review integrates current findings, highlighting the need for deeper investigation into cross-organ interactions and early microbial exposures to understand childhood asthma pathophysiology.
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Affiliation(s)
- Céline Pattaroni
- Department of Immunology, School of Translational MedicineMonash UniversityMelbourneVictoriaAustralia
| | - Benjamin J. Marsland
- Department of Immunology, School of Translational MedicineMonash UniversityMelbourneVictoriaAustralia
| | - Nicola L. Harris
- Department of Immunology, School of Translational MedicineMonash UniversityMelbourneVictoriaAustralia
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10
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Hirata Y, Sakuma Y, Ogiso H, Nagai R, Aizawa K. Targeted Plasma Bile Acid Metabolomic Analysis in Metabolic Dysfunction-Associated Steatohepatitis and Alcoholic Hepatitis. Biomedicines 2024; 13:78. [PMID: 39857662 PMCID: PMC11762544 DOI: 10.3390/biomedicines13010078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 12/27/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
Background: Even though many metabolic liver diseases can now be diagnosed using blood tests and diagnostic imaging, early diagnosis remains difficult. Understanding mechanisms contributing to the progression from Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Alcoholic Hepatitis (AH) to cirrhosis is critical to reduce the burden of end-stage liver disease. Monitoring individual bile acids has been proposed as a way to distinguish various liver disorders. Methods: This study explored bile acid profiles in patients with MASH and AH. Plasma samples from patients with MASH, AH, and a control group were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify bile acid concentrations. Targeted metabolomic analysis was performed to compare bile acid levels between the hepatitis and control groups. Results: Concentrations of ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) were significantly elevated in the hepatitis group. Correlation analysis revealed strong positive relationships between the total and direct bilirubin levels and TUDCA and GCDCA. Aspartate aminotransferase (AST) showed strong positive correlations with TCDCA and GCDCA. Child-Pugh score, Fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score were positively correlated with GCA, whereas the aspartate aminotransferase-to-platelet ratio correlated with TCA, TCDCA, and GCA. The model for end-stage liver disease (MELD) score showed a strong positive correlation with GCDCA. Implications: GCDCA may serve as a predictive biomarker for liver damage, potentially enabling early diagnosis and targeted intervention in patients with MASH and AH.
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Affiliation(s)
- Yuta Hirata
- Division of Gastroenterological, Department of Surgery, General and Transplant Surgery, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan
| | - Yasunaru Sakuma
- Division of Gastroenterological, Department of Surgery, General and Transplant Surgery, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan
| | - Hideo Ogiso
- Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan
| | - Ryozo Nagai
- Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan
| | - Kenichi Aizawa
- Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Shimotsuke 329-0498, Tochigi, Japan
- Clinical Pharmacology Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Tochigi, Japan
- Division of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Tochigi, Japan
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11
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Jiang C, Zhan Q, Zeng C. The 5-HT-related gut-brain axis in obesity. Life Sci 2024; 358:123171. [PMID: 39447731 DOI: 10.1016/j.lfs.2024.123171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 08/22/2024] [Accepted: 10/20/2024] [Indexed: 10/26/2024]
Abstract
AIMS The incidence of obesity increases annually. It is closely related to the occurrence of cardiovascular diseases, malignant tumors, etc., and has become a major global health problem. 5-hydroxytryptamine (5-HT), a multifunctional monoamine neurotransmitter, is dispersed throughout the central nervous system and digestive tract. It is intimately related to the mechanism of obesity. MATERIALS AND METHODS PubMed, Web of Science and Embase were carefully searched. We collected articles that are closely related to 5-HT, the gut-brain axis, and obesity. KEY FINGDINGS The gut microbiota not only influences nutrient metabolism but also centrally meditates appetite and mood regulation. The gut-brain axis, a system connecting the gut and the brain, is known to participate in two-way communication between the gut flora and the central nervous system. SIGNIFICANCE There have been few reports on whether peripheral and central 5-HT interact bidirectionally via the gut-brain axis and jointly play a role in the pathogenesis of obesity. In this review, we summarize the rationale for the contribution of the 5-HT-related gut-brain axis to the development of obesity and explore feasible signaling pathways, which elucidates new targets for preventing and treating obesity.
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Affiliation(s)
- Chaoyong Jiang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Qiong Zhan
- Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha 410011, China; Clinical Medical Research Center for Stroke Prevention and Treatment of Hunan Province, Department of Neurology, the Second Xiangya Hospital, Central South University, Changsha 410011, China
| | - Chang Zeng
- Health Management Center, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
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12
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Luo M, Han Y, Chen Y, Du H, Chen B, Gao Z, Wang Q, Cao Y, Xiao H. Unveiling the role of gut microbiota in curcumin metabolism using antibiotic-treated mice. Food Chem 2024; 460:140706. [PMID: 39096800 DOI: 10.1016/j.foodchem.2024.140706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/23/2024] [Accepted: 07/28/2024] [Indexed: 08/05/2024]
Abstract
Curcumin might exert its therapeutic effects by interacting with gut microbiota. However, the role of gut microbiota in curcumin metabolism in vivo remains poorly understood. To address this, we used antibiotics to deplete gut microbiota and compared curcumin metabolism in control and antibiotic-treated mice. Using Q-TOF and triple quadrupole mass spectrometry, we identified and quantified curcumin metabolites, revealing distinct metabolic pathways in these two mice groups. The novel metabolites, hexahydro-dimethyl-curcumin and hexahydro-didemethyl-curcumin were exclusively derived from gut microbiota. Additionally, gut bacteria deconjugated curcumin metabolites back into their bioactive forms. Moreover, control mice exhibited significantly lower curcumin degradation, suggesting a protective role of gut microbiota against degradation. In conclusion, our results indicated that gut microbiota might enhance the effectiveness of curcumin by deconjugation, production of active metabolites, and protection against degradation in the large intestine. This study enhances our understanding of the interactions between curcumin and gut microbiota.
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Affiliation(s)
- Minna Luo
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Yanhui Han
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Yilu Chen
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Hengjun Du
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Bin Chen
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Zili Gao
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Qi Wang
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - Yong Cao
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou, Guangdong, China
| | - Hang Xiao
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA.
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13
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Shayista H, Prasad MN, Raj SN, Ranjini H, Manju K, Baker S. Mechanistic overview of gut microbiota and mucosal pathogens with respect to cardiovascular diseases. THE MICROBE 2024; 5:100160. [DOI: 10.1016/j.microb.2024.100160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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14
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Bello AT, Sarafian MH, Wimborne EA, Middleton B, Revell VL, Raynaud FI, Chowdhury NR, van der Veen DR, Skene DJ, Swann JR. Exposing 24-hour cycles in bile acids of male humans. Nat Commun 2024; 15:10014. [PMID: 39562795 PMCID: PMC11576969 DOI: 10.1038/s41467-024-53673-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 10/17/2024] [Indexed: 11/21/2024] Open
Abstract
Bile acids are trans-genomic molecules arising from the concerted metabolism of the human host and the intestinal microbiota and are important for digestion, energy homeostasis and metabolic regulation. While diurnal variation has been demonstrated in the enterohepatic circulation and the gut microbiota, existing human data are poorly resolved, and the influence of the host circadian system has not been determined. Using entrained laboratory protocols, we demonstrate robust daily rhythms in the circulating bile acid pool in healthy male participants. We identify temporal relationships between bile acids and plasma lipids and show that these relationships are lost following sleep deprivation. We also highlight that bile acid rhythmicity is predominantly lost when environmental timing cues are held constant. Here we show that the environment is a stronger determinant of these temporal dynamics than the intrinsic circadian system of the host. This has significance for the intimate relationship between circadian timing and metabolism.
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Affiliation(s)
- Adesola T Bello
- Section of Nutrition, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | | | - Elizabeth A Wimborne
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Benita Middleton
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
| | - Victoria L Revell
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
- Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Florence I Raynaud
- Centre for Cancer Drug Discovery, Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK
| | - Namrata R Chowdhury
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
| | - Daan R van der Veen
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
| | - Debra J Skene
- Chronobiology Section, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK
| | - Jonathan R Swann
- Section of Nutrition, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.
- School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK.
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15
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Shah SAUR, Tang B, He D, Hao Y, Ahmad M, Nabi G, McLaughlin R, Wang C, Kou Z, Wang K. Effect of calf separation on gut microbiome and fecal metabolome of mother in the captive Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis). Int Microbiol 2024:10.1007/s10123-024-00613-8. [PMID: 39532805 DOI: 10.1007/s10123-024-00613-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 11/01/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024]
Abstract
Social separation, or the absence of social support, can cause physical and psychological health issues. Social separation is crucial for the welfare of the Yangtze finless porpoise (YFP) in captivity because they face many challenges like frequent social separation, noise from visitors, and animal replacement, which can cause psychological and physiological stress. This research is aimed at assessing the potential negative impacts of social separation on the gut microbiome and metabolome of captive YFP, focusing on the potential imbalances caused by mother-calf separation. The study found that social separation did not alter the alpha and beta diversity of the gut microbes but increased the abundance of disease-associated taxa such as Romboutsia, Terrisporobacter, and Clostridium_sensu_stricto_13 in the MC (mother-calf) group while increasing Paeniclostridium and Clostridium_sensu_stricto_1 associated with host health in the MS (mother-separated) group. The fecal metabolome underwent significant changes during social separation, with stress-associated metabolites like kainic acid, phenethylamine glucuronide, and paxilline upregulated in the MC group and host health-associated metabolites like butyric acid, 6-hydroxyhexanoic acid, and fosinopril downregulated in the MS group. In addition, there was a strong association between the fecal microbiome and the metabolome of captive YFPs. The study enhances our comprehension of the detrimental effects of social separation, which result in disruptions in the gut microbiome and fecal metabolome. The study is aimed at introducing a new method for assessing the health and welfare of endangered mammals in captivity.
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Affiliation(s)
- Syed Ata Ur Rahman Shah
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Bin Tang
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
- University of Chinese Academy of Sciences, Beijing, China
- National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Dekui He
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
- National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Yujiang Hao
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
- National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China.
| | - Maaz Ahmad
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Ghulam Nabi
- Department of Zoology, Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan
| | - Richard McLaughlin
- School of Liberal Arts and Sciences, Gateway Technical College, Kenosha, WI, 53144, USA
| | - Chaoqun Wang
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Zhangbing Kou
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
| | - Kexiong Wang
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China
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Gillard J, Roumain M, Picalausa C, Thibaut MM, Clerbaux LA, Tailleux A, Staels B, Muccioli GG, Bindels LB, Leclercq IA. A gut microbiota-independent mechanism shapes the bile acid pool in mice with MASH. JHEP Rep 2024; 6:101148. [PMID: 39741697 PMCID: PMC11686050 DOI: 10.1016/j.jhepr.2024.101148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 06/02/2024] [Accepted: 06/13/2024] [Indexed: 01/03/2025] Open
Abstract
Background & Aims An imbalance between primary and secondary bile acids contributes to the development of metabolic dysfunction-associated steatohepatitis (MASH). The precise mechanisms underlying changes in the bile acid pool in MASH remain to be identified. As gut bacteria convert primary bile acids to secondary bile acids, we investigated the contribution of the gut microbiota and its metabolizing activities to bile acid alterations in MASH. Methods To disentangle the influence of MASH from environmental and dietary factors, high-fat diet fed foz/foz mice were compared with their high-fat diet fed wildtype littermates. We developed functional assays (stable isotope labeling and in vitro experiments) to extend the analyses beyond a mere study of gut microbiota composition (16S rRNA gene sequencing). Key findings were confirmed in C57BL/6J mice were fed a Western and high-fructose diet, as an independent mouse model of MASH. Results Although mice with MASH exhibited lower levels of secondary 7α-dehydroxylated bile acids (3.5-fold lower, p = 0.0008), the gut microbial composition was similar in mice with and without MASH. Similar gut microbial bile salt hydrolase and 7α-dehydroxylating activities could not explain the low levels of secondary 7α-dehydroxylated bile acids. Furthermore, the 7α-dehydroxylating activity was unaffected by Clostridium scindens administration in mice with a non-standardized gut microbiota. By exploring alternative mechanisms, we identified an increased bile acid 7α-rehydroxylation mediated by liver CYP2A12 and CYP2A22 enzymes (4.0-fold higher, p <0.0001), that reduces secondary 7α-dehydroxylated bile acid levels in MASH. Conclusions This study reveals a gut microbiota-independent mechanism that alters the level of secondary bile acids and contributes to the development of MASH in mice. Impact and implications Although changes in bile acid levels are implicated in the development of metabolic dysfunction-associated steatohepatitis (MASH), the precise mechanisms underpinning these alterations remain elusive. In this study, we investigated the mechanisms responsible for the changes in bile acid levels in mouse models of MASH. Our results support that neither the composition nor the metabolic activity of the gut microbiota can account for the alterations in the bile acid pool. Instead, we identified hepatic 7α-rehydroxylation of secondary bile acids as a gut microbiota-independent factor contributing to the reduced levels of secondary bile acids in mice with MASH. Further investigation is warranted to understand bile acid metabolism and its physiological implications in clinical MASH. Nonetheless, our findings hold promise for exploring novel therapeutic interventions for MASH.
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Affiliation(s)
- Justine Gillard
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Martin Roumain
- Bioanalysis and Pharmacology of Bioactive Lipids, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Corinne Picalausa
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
| | - Morgane M. Thibaut
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Laure-Alix Clerbaux
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
| | - Anne Tailleux
- University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Bart Staels
- University of Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Giulio G. Muccioli
- Bioanalysis and Pharmacology of Bioactive Lipids, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
| | - Laure B. Bindels
- Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium
- Welbio department, WEL Research Institute, Wavre, Belgium
| | - Isabelle A. Leclercq
- Laboratory of Hepato-Gastroenterology, Institute of Experimental and Clinical Research, Université Catholique de Louvain, Brussels, Belgium
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17
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Meng S, Xing S, Xu H, Li J, Jiang Y, He H, Cai H, Li M. Integrated analysis of intestinal microbial community and muscle transcriptome profile in rabbits. Anim Biotechnol 2024; 35:2387015. [PMID: 39145993 DOI: 10.1080/10495398.2024.2387015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
Intestinal microbial community plays an important part in maintaining health and skeletal muscle development in livestock. This study is the first of its kind in the world. In order to better understand the relationship between gut microbiota and gene expression in skeletal muscle of rabbits, caecum contents and longissimus dorsi tissues of rabbits at 0 d (S1), 35 d (S2) and 70d (S3) were collected and subjected for 16S rRNA sequencing and transcriptome sequencing. Our results showed that, among three groups of rabbits, Firmicutes and Bacteroidetes were the dominant phyla at the phylum level, while Akmansia, Bacteroides and Ruminobacter were the dominant genera at the genus level, and the relative abundance of Akmansia and Bacteroides increased firstly and then decreased from 0 d to 70 d. By analyzing the transcriptome sequencing data, we identified 2866, 2446 and 4541 differentially expressed genes (DEGs) in S1 vs S2, S2 vs S3 and S1 vs S3 groups, respectively. Finally, we performed correlation analysis between gut microbiota and the expression levels of muscle development-related genes of rabbits at 0 d and 70 d. Compared with 0 day old rabbits, in 70 day old rabbits Acinetobacter and Cronbacter with decreased abundance, and Ruminococcaceae_UCG-014 and Ruminococcus_1 with increase abundance is beneficial to caecum health in rabbits. These results will lay a foundation for further re-searches about the relationship between caecum microflora and muscle development in rabbits.
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Affiliation(s)
- Shengbo Meng
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
| | - Shanshan Xing
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
| | - Huifen Xu
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
| | - Jing Li
- Animal Health Supervision Institute of Biyang, Henan, P.R. China
| | - Yixuan Jiang
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
| | - Hui He
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
| | - Hanfang Cai
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
| | - Ming Li
- College of Animal Science and Technology, Henan Agricultural University, Zhengzhou, P.R. China
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18
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Li T, Chiang JYL. Bile Acid Signaling in Metabolic and Inflammatory Diseases and Drug Development. Pharmacol Rev 2024; 76:1221-1253. [PMID: 38977324 PMCID: PMC11549937 DOI: 10.1124/pharmrev.124.000978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/10/2024] Open
Abstract
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders. SIGNIFICANCE STATEMENT: Bile acids facilitate biliary cholesterol solubilization and dietary lipid absorption, regulate host metabolism and immunity, and modulate gut microbiome. Targeting bile acid metabolism and signaling holds promise for treating metabolic and inflammatory diseases.
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Affiliation(s)
- Tiangang Li
- Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (T.L.); and Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (J.Y.L.C.)
| | - John Y L Chiang
- Department of Biochemistry and Physiology, Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (T.L.); and Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio (J.Y.L.C.)
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19
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Wang M, Ren F, Zhou Y, He Y, Du T, Tan Y. Age-related sarcopenia and altered gut microbiota: A systematic review. Microb Pathog 2024; 195:106850. [PMID: 39142365 DOI: 10.1016/j.micpath.2024.106850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 07/28/2024] [Accepted: 08/12/2024] [Indexed: 08/16/2024]
Abstract
BACKGROUND Sarcopenia, a hallmark of age-related muscle function decline, significantly impacts elderly physical health. This systematic review aimed to investigate the impact of gut microbiota on sarcopenia. METHODS Publications up to September 24, 2023 were scrutinized on four databases - PubMed, Web of Science, Cochrane Library, and Embase - using relevant keywords. Non-English papers were disregarded. Data regarding gut microbiota alterations in sarcopenic patients/animal models were collected and examined. RESULTS Thirteen human and eight animal studies were included. The human studies involved 732 sarcopenic or potentially sarcopenic participants (aged 57-98) and 2559 healthy subjects (aged 54-84). Animal studies encompassed five mouse and three rat experiments. Results indicated an increase in opportunistic pathogens like Enterobacteriaceae, accompanied by changes in several metabolite-related organisms. For example, Bacteroides fluxus related to horse uric acid metabolism exhibited increased abundance. However, Roseburia, Faecalibacterium, Faecalibacterium prausnitzii, Eubacterium retale, Akkermansiaa, Coprococcus, Clostridium_XIVa, Ruminococcaceae, Bacteroides, Clostridium, Eubacterium involved in urolithin A production, and Lactobacillus, Bacteroides, and Clostridium associated with bile acid metabolism displayed decreased abundance. CONCLUSIONS Age-related sarcopenia and gut microbiota alterations are intricately linked. Short-chain fatty acid metabolism, urolithin A, and bile acid production may be pivotal factors in the gut-muscle axis pathway. Supplementation with beneficial metabolite-associated microorganisms could enhance muscle function, mitigate muscle atrophy, and decelerate sarcopenia progression.
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Affiliation(s)
- Mengyu Wang
- Department of Medical Microbiology, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China
| | - Fangyuan Ren
- Department of Obstetrics, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, 410017, China
| | - Yan Zhou
- Department of Obstetrics, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Changsha, 410017, China
| | - Yuan He
- Department of Medical Microbiology, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China
| | - Taorui Du
- Department of Medical Microbiology, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China
| | - Yurong Tan
- Department of Medical Microbiology, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
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Murugan R, Priya PS, Boopathi S, Haridevamuthu B, Kumar TTA, Arockiaraj J. Unraveling the etiology of shrimp diseases: a review through the perspectives of gut microbial dynamics. AQUACULTURE INTERNATIONAL 2024; 32:5579-5602. [DOI: 10.1007/s10499-024-01437-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 02/12/2024] [Indexed: 01/12/2025]
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Ren L, Ju F, Liu S, Cai Y, Gang X, Wang G. New Perspectives on Obesity-Associated Nephropathy from Pathophysiology to Therapeutics: Revealing the Promise of GLP-1 RA Therapy. Drug Des Devel Ther 2024; 18:4257-4272. [PMID: 39347536 PMCID: PMC11437658 DOI: 10.2147/dddt.s476815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 09/10/2024] [Indexed: 10/01/2024] Open
Abstract
Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues.
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Affiliation(s)
- Linan Ren
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Feng Ju
- Department of Orthopedics, Yuci District People’s Hospital, Yuci, Shanxi, 030600, People’s Republic of China
| | - Siyuan Liu
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Yunjia Cai
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
- Institute of Translational Medicine, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China
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Xiao K, Li H, Li Y, Zhan B, Fang X, Zhao B, Zhang X, Wu Y, Wang F, Jia Y. Protective effects and mechanism of Sangyu granule on acetaminophen-induced liver injury in mice. JOURNAL OF ETHNOPHARMACOLOGY 2024; 331:118282. [PMID: 38701935 DOI: 10.1016/j.jep.2024.118282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Revised: 04/23/2024] [Accepted: 04/30/2024] [Indexed: 05/06/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The Sang Yu granule (SY), a traditional Chinese medicine prescription of Xijing Hospital, was developed based on the Guanyin powder in the classical prescription "Hong's Collection of Proven Prescriptions" and the new theory of modern Chinese medicine. It has been proved to have a certain therapeutic effect on drug-induced liver injury (DILI), but the specific mechanism of action is still unclear. AIM OF STUDY Aim of the study was to explore the effect of SangYu granule on treating drug-induced liver injury induced by acetaminophen in mice. MATERIALS AND METHODS The chemical composition of SY, serum, and liver tissue was analyzed using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To assess hepatic function, measurements were taken using kits for total bile acids, as well as serum AST, ALT, and ALP activity. Concentrations of IL-1β and TNF-α in serum were quantified using ELISA kits. Transcriptome Sequencing Analysis and 2bRAD-M microbial diversity analysis were employed to evaluate gene expression variance in liver tissue and fecal microbiota diversity among different groups, respectively. Western blotting was performed to observe differences in the activation levels of FXR, SHP, CYP7A1 and PPARα in the liver, and the levels of FXR and FGF-15 genes and proteins in the ileum of mice. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to investigate the potential therapeutic effect of administering the intestinal microbial suspension from mice treated with SY on drug-induced liver injury. RESULTS SY treatment exhibited significant hepatoprotective effects in mice, effectively ameliorating drug-induced liver injury while concurrently restoring intestinal microbial dysbiosis. Furthermore, SY administration demonstrated a reduction in the concentration of total bile acids, the expression of FXR and SHP proteins in the liver was up-regulated, CYP7A1 protein was down-regulated, and the expressions of FXR and FGF-15 proteins in the ileum were up-regulated. However, no notable impact on PPARα was observed. Furthermore, results from FMT experiments indicated that the administration of fecal suspensions derived from mice treated with SY did not yield any therapeutic benefits in the context of drug-induced liver injury. CONCLUSION The aforementioned findings strongly suggest that SY exerts a pronounced ameliorative effect on drug-induced liver injury through its ability to modulate the expression of key proteins involved in bile acid secretion, thereby preserving hepato-enteric circulation homeostasis.
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Affiliation(s)
- Kexin Xiao
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China; College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China
| | - Hongyu Li
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China; College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China
| | - Yuening Li
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China; College of life sciences, Northwestern University, Xi'an, 710069, China
| | - Bo Zhan
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China; College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China
| | - Xiaohua Fang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China
| | - Bingjie Zhao
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China; College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China
| | - Xiaofei Zhang
- College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China.
| | - Yumei Wu
- Department of Pharmacology, Air Force Medical University, Xi'an, 710032, China.
| | - Fan Wang
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China.
| | - Yanyan Jia
- Department of Pharmacy, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi Province, China; College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, China.
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Yaghmaei H, Nojoumi SA, Soltanipur M, Yarmohammadi H, Mirhosseini SM, Rezaei M, Jalali Nadoushan M, Siadat SD. The role of gut microbiota in non-alcoholic fatty liver disease pathogenesis. OBESITY MEDICINE 2024; 50:100551. [DOI: 10.1016/j.obmed.2024.100551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
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Zhao J, Fang Z. Alterations of the gut microbiota and metabolites by ShenZhu TiaoPi granule alleviates hyperglycemia in GK rats. Front Microbiol 2024; 15:1420103. [PMID: 39372266 PMCID: PMC11451479 DOI: 10.3389/fmicb.2024.1420103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/29/2024] [Indexed: 10/08/2024] Open
Abstract
ShenZhu TiaoPi granule (STG) is a compound prescription that is used in Chinese medicine for the treatment of type 2 diabetes mellitus (T2DM). Previous studies have indicated a hypoglycaemic effect, but the underlying mechanism remains unclear. Goto-Kakizaki (GK) rats were used to establish an in vivo T2DM model (Mod). The metformin (Met) and STG treatment time was 12 weeks. Fasting blood glucose (FBG) and insulin levels and the area under the glucose curve (GAUC) were measured. Intestinal pathology and permeability were observed. Microbial diversity analysis and metabolomics were used to investigate the underlying mechanisms. Compared with the Con group, the T2DM Mod group presented significant differences in weight, FBG, GAUC, and homeostasis model assessment-insulin resistance (HOMA-IR) indices (p < 0.01). Met and STG improved these indicators (p < 0.01). The pathological morphology and zonula occludens 1 protein levels in the intestines of the Mod group of rats were altered, leading to increases in the lipopolysaccharide (LPS) and interleukin-1β (IL-1β) levels. In the Met and STG groups, the intestinal conditions improved, and the LPS and IL-1β levels significantly decreased (p < 0.01). Changes in the gut microbiota and metabolites occurred in the Mod group. In the STG group, the abundance of Intestinimonas increased, and the abundance of Eubacterium coprostanoligenes decreased significantly (p < 0.05). Moreover, STG also altered 2-deoxyglucose, beta-muricholic acid and dioxolithocholic acid production. In addition, the main metabolic pathways affected by STG were bile acid biosynthesis and cholesterol metabolism. Intestinimonas, D-maltose_and_alpha-lactose may be potential biomarkers for the effects of STG. STG alleviates hyperglycaemia via the gut microbiota and metabolites in GK rats.
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Affiliation(s)
- Jindong Zhao
- Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Center for Xin'an Medicine and Modernizatison of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Zhaohui Fang
- Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
- Center for Xin'an Medicine and Modernizatison of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China
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Pi Y, Fang M, Li Y, Cai L, Han R, Sun W, Jiang X, Chen L, Du J, Zhu Z, Li X. Interactions between Gut Microbiota and Natural Bioactive Polysaccharides in Metabolic Diseases: Review. Nutrients 2024; 16:2838. [PMID: 39275156 PMCID: PMC11397228 DOI: 10.3390/nu16172838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/16/2024] [Accepted: 08/22/2024] [Indexed: 09/16/2024] Open
Abstract
The gut microbiota constitutes a complex ecosystem, comprising trillions of microbes that have co-evolved with their host over hundreds of millions of years. Over the past decade, a growing body of knowledge has underscored the intricate connections among diet, gut microbiota, and human health. Bioactive polysaccharides (BPs) from natural sources like medicinal plants, seaweeds, and fungi have diverse biological functions including antioxidant, immunoregulatory, and metabolic activities. Their effects are closely tied to the gut microbiota, which metabolizes BPs into health-influencing compounds. Understanding how BPs and gut microbiota interact is critical for harnessing their potential health benefits. This review provides an overview of the human gut microbiota, focusing on its role in metabolic diseases like obesity, type II diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular diseases. It explores the basic characteristics of several BPs and their impact on gut microbiota. Given their significance for human health, we summarize the biological functions of these BPs, particularly in terms of immunoregulatory activities, blood sugar, and hypolipidemic effect, thus providing a valuable reference for understanding the potential benefits of natural BPs in treating metabolic diseases. These properties make BPs promising agents for preventing and treating metabolic diseases. The comprehensive understanding of the mechanisms by which BPs exert their effects through gut microbiota opens new avenues for developing targeted therapies to improve metabolic health.
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Affiliation(s)
- Yu Pi
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Miaoyu Fang
- Nutrilite Health Institute, Amway (Shanghai) Innovation & Science Co., Ltd., Shanghai 201203, China
| | - Yanpin Li
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Long Cai
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Ruyi Han
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Wenjuan Sun
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Xianren Jiang
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Liang Chen
- Nutrilite Health Institute, Amway (Shanghai) Innovation & Science Co., Ltd., Shanghai 201203, China
| | - Jun Du
- Nutrilite Health Institute, Amway (Shanghai) Innovation & Science Co., Ltd., Shanghai 201203, China
| | - Zhigang Zhu
- Nutrilite Health Institute, Amway (Shanghai) Innovation & Science Co., Ltd., Shanghai 201203, China
| | - Xilong Li
- Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
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Li X, Lu C, Mao X, Fan J, Yao J, Jiang J, Wu L, Ren J, Shen J. Bibliometric analysis of research on gut microbiota and bile acids: publication trends and research frontiers. Front Microbiol 2024; 15:1433910. [PMID: 39234549 PMCID: PMC11371755 DOI: 10.3389/fmicb.2024.1433910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/07/2024] [Indexed: 09/06/2024] Open
Abstract
The gut microbiota is widely regarded as a "metabolic organ" that could generate myriad metabolites to regulate human metabolism. As the microbiota metabolites, bile acids (BAs) have recently been identified as the critical endocrine molecules that mediate the cross-talk between the host and intestinal microbiota. This study provided a comprehensive insight into the gut microbiota and BA research through bibliometric analysis from 2003 to 2022. The publications on this subject showed a dramatic upward trend. Although the USA and China have produced the most publications, the USA plays a dominant role in this expanding field. Specifically, the University of Copenhagen was the most productive institution. Key research hotspots are the gut-liver axis, short-chain fatty acids (SCFAs), cardiovascular disease (CVD), colorectal cancer (CRC), and the farnesoid x receptor (FXR). The molecular mechanisms and potential applications of the gut microbiota and BAs in cardiometabolic disorders and gastrointestinal cancers have significant potential for further research.
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Affiliation(s)
- Xin Li
- Department of General Medicine and Geriatrics, Linping Campus, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Department of General Practice, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Can Lu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Department of Medical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xue Mao
- Department of General Medicine and Geriatrics, Linping Campus, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiahong Fan
- Department of General Medicine and Geriatrics, Linping Campus, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jianting Yao
- Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Jingjie Jiang
- Department of General Medicine and Geriatrics, Linping Campus, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Lele Wu
- Department of General Medicine and Geriatrics, Linping Campus, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jingjing Ren
- Department of General Practice, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jun Shen
- Department of General Medicine and Geriatrics, Linping Campus, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China
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Roth K, Yang Z, Agarwal M, Birbeck J, Westrick J, Lydic T, Gurdziel K, Petriello MC. Exposure of Ldlr-/- Mice to a PFAS Mixture and Outcomes Related to Circulating Lipids, Bile Acid Excretion, and the Intestinal Transporter ASBT. ENVIRONMENTAL HEALTH PERSPECTIVES 2024; 132:87007. [PMID: 39177951 PMCID: PMC11343043 DOI: 10.1289/ehp14339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 07/24/2024] [Accepted: 07/29/2024] [Indexed: 08/24/2024]
Abstract
BACKGROUND Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced impacts on enterohepatic circulation may play a critical role in cardiovascular risk. OBJECTIVES Using a mouse model with high levels of low-density and very low-density lipoprotein (LDL and VLDL, respectively) cholesterol and aortic lesion development similar to humans, the present study investigated mechanisms linking exposure to a PFAS mixture with increased cholesterol. METHODS Male and female L d l r - / - mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFHxS, PFNA, GenX), each at a concentration of 2 mg / L , for 7 wk. Blood was collected longitudinally for cholesterol measurements, and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA sequencing. RESULTS After 7 wk of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1.5 μ g / mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1.7 μ g / mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. Total circulating cholesterol levels were higher in PFAS-exposed mice after 7 wk (352 mg / dL vs. 415 mg / dL in female mice and 392 mg / dL vs. 488 mg / dL in male mice exposed to vehicle or PFAS, respectively). Total circulating bile acid levels were higher in PFAS-exposed mice (2,978 pg / μ L vs. 8,496 pg / μ L in female mice and 1,960 pg / μ L vs. 4,452 pg / μ L in male mice exposed to vehicle or PFAS, respectively). In addition, total fecal bile acid levels were lower in PFAS-exposed mice (1,797 ng / mg vs. 682 ng / mg in females and 1,622 ng / mg vs. 670 ng / mg in males exposed to vehicle or PFAS, respectively). In the ileum, expression levels of the apical sodium-dependent bile acid transporter (ASBT) were higher in PFAS-exposed mice. DISCUSSION Mice exposed to a PFAS mixture displayed higher circulating cholesterol and bile acids perhaps due to impacts on enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk following PFAS exposure. https://doi.org/10.1289/EHP14339.
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Affiliation(s)
- Katherine Roth
- Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Zhao Yang
- Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA
| | - Manisha Agarwal
- Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan, USA
| | - Johnna Birbeck
- Department of Chemistry, Lumigen Instrumentation Center, Wayne State University, Detroit, Michigan, USA
| | - Judy Westrick
- Department of Chemistry, Lumigen Instrumentation Center, Wayne State University, Detroit, Michigan, USA
| | - Todd Lydic
- Department of Physiology, Michigan State University, East Lansing, Michigan, USA
| | - Katherine Gurdziel
- Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA
- Genome Sciences Core, Wayne State University, Detroit, Michigan, USA
| | - Michael C. Petriello
- Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan, USA
- Department of Pharmacology, School of Medicine, Wayne State University, Detroit, Michigan, USA
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Dicks L, Schuh-von Graevenitz K, Prehn C, Sadri H, Murani E, Hosseini Ghaffari M, Häussler S. Bile acid profiles and mRNA abundance of bile acid-related genes in adipose tissue of dairy cows with high versus normal body condition. J Dairy Sci 2024; 107:6288-6307. [PMID: 38490538 DOI: 10.3168/jds.2024-24346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/14/2024] [Indexed: 03/17/2024]
Abstract
Besides their lipid-digestive role, bile acids (BA) influence overall energy homeostasis, such as glucose and lipid metabolism. We hypothesized that BA along with their receptors, regulatory enzymes, and transporters are present in subcutaneous adipose tissue (scAT). In addition, we hypothesized that their mRNA abundance varies with the body condition of dairy cows around calving. Therefore, we analyzed BA in serum and scAT as well as the mRNA abundance of BA-related enzymes, transporters, and receptors in scAT during the transition period in cows with different body conditions around calving. In a previously established animal model, 38 German Holstein cows were divided into either a high (HBCS; n = 19) or normal BCS (NBCS; n = 19) group based on their BCS and back-fat thickness (BFT). Cows were fed different diets to achieve the targeted differences in BCS and BFT (NBCS: BCS <3.5, BFT <1.2 cm; HBCS: BCS >3.75, BFT >1.4 cm) until dry-off at 7 wk antepartum. During the dry period and subsequent lactation, both groups were fed the same diets according to their energy demands. Using a targeted metabolomics approach via liquid chromatography-electrospray ionization-MS /MS, BA were analyzed in serum and scAT at wk -7, 1, 3, and 12 relative to parturition. In serum, 15 BA were observed: cholic acid (CA), chenodeoxycholic acid (CDCA), glycocholic acid (GCA), taurocholic acid (TCA), glycochenodeoxycholic acid (GCDCA), taurochenodeoxycholic acid, deoxycholic acid (DCA), lithocholic acid, glycodeoxycholic acid (GDCA), glycolithocholic acid, taurodeoxycholic acid, taurolithocholic acid, β-muricholic acid, tauromuricholic acid (sum of α and β), and glycoursodeoxycholic acid, whereas in scAT 7 BA were detected: CA, GCA, TCA, GCDCA, taurochenodeoxycholic acid, GDCA, and taurodeoxycholic acid. In serum and scAT samples, the primary BA CA and its conjugate GCA were predominantly detected. Increasing serum concentrations of CA, CDCA, TCA, GCA, GCDCA, DCA, and β-muricholic acid with the onset of lactation might be related to the increasing DMI after parturition. Furthermore, serum concentrations of CA, CDCA, GCA, DCA, GCDCA, TCA, lithocholic acid, and GDCA were lower in HBCS cows compared with NBCS cows, concomitant with increased lipolysis in HBCS cows. The correlation between CA in serum and scAT may point to the transport of CA across cell membranes. Overall, the findings of the present study suggest a potential role of BA in lipid metabolism depending on the body condition of periparturient dairy cows.
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Affiliation(s)
- Lena Dicks
- Institute of Animal Science, Physiology Unit, University of Bonn, 53115 Bonn, Germany
| | - Katharina Schuh-von Graevenitz
- Department of Life Sciences and Engineering, Animal Nutrition and Hygiene Unit, University of Applied Sciences Bingen, 55411 Bingen am Rhein, Germany
| | - Cornelia Prehn
- Helmholtz Zentrum München, German Research Center for Environmental Health, Metabolomics and Proteomics Core, 85764 Neuherberg, Germany
| | - Hassan Sadri
- Department of Clinical Science, Faculty of Veterinary Medicine, University of Tabriz, 516616471 Tabriz, Iran
| | - Eduard Murani
- Research Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
| | | | - Susanne Häussler
- Institute of Animal Science, Physiology Unit, University of Bonn, 53115 Bonn, Germany.
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Mohanty I, Allaband C, Mannochio-Russo H, El Abiead Y, Hagey LR, Knight R, Dorrestein PC. The changing metabolic landscape of bile acids - keys to metabolism and immune regulation. Nat Rev Gastroenterol Hepatol 2024; 21:493-516. [PMID: 38575682 DOI: 10.1038/s41575-024-00914-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/14/2024] [Indexed: 04/06/2024]
Abstract
Bile acids regulate nutrient absorption and mitochondrial function, they establish and maintain gut microbial community composition and mediate inflammation, and they serve as signalling molecules that regulate appetite and energy homeostasis. The observation that there are hundreds of bile acids, especially many amidated bile acids, necessitates a revision of many of the classical descriptions of bile acids and bile acid enzyme functions. For example, bile salt hydrolases also have transferase activity. There are now hundreds of known modifications to bile acids and thousands of bile acid-associated genes, especially when including the microbiome, distributed throughout the human body (for example, there are >2,400 bile salt hydrolases alone). The fact that so much of our genetic and small-molecule repertoire, in both amount and diversity, is dedicated to bile acid function highlights the centrality of bile acids as key regulators of metabolism and immune homeostasis, which is, in large part, communicated via the gut microbiome.
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Affiliation(s)
- Ipsita Mohanty
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Celeste Allaband
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA
| | - Helena Mannochio-Russo
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Yasin El Abiead
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Lee R Hagey
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
| | - Pieter C Dorrestein
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
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Yang Y, Chi L, Hsiao YC, Lu K. Sex-specific effects of gut microbiome on shaping bile acid metabolism. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.06.27.601003. [PMID: 38979196 PMCID: PMC11230406 DOI: 10.1101/2024.06.27.601003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/10/2024]
Abstract
Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations between sex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sexspecific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum. Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes.
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Affiliation(s)
- Yifei Yang
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
| | - Liang Chi
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
| | - Yun-Chung Hsiao
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
| | - Kun Lu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC, 27599, United States
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31
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Lu ZF, Hsu CY, Younis NK, Mustafa MA, Matveeva EA, Al-Juboory YHO, Adil M, Athab ZH, Abdulraheem MN. Exploring the significance of microbiota metabolites in rheumatoid arthritis: uncovering their contribution from disease development to biomarker potential. APMIS 2024; 132:382-415. [PMID: 38469726 DOI: 10.1111/apm.13401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 02/27/2024] [Indexed: 03/13/2024]
Abstract
Rheumatoid arthritis (RA) is a multifaceted autoimmune disorder characterized by chronic inflammation and joint destruction. Recent research has elucidated the intricate interplay between gut microbiota and RA pathogenesis, underscoring the role of microbiota-derived metabolites as pivotal contributors to disease development and progression. The human gut microbiota, comprising a vast array of microorganisms and their metabolic byproducts, plays a crucial role in maintaining immune homeostasis. Dysbiosis of this microbial community has been linked to numerous autoimmune disorders, including RA. Microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), tryptophan derivatives, Trimethylamine-N-oxide (TMAO), bile acids, peptidoglycan, and lipopolysaccharide (LPS), exhibit immunomodulatory properties that can either exacerbate or ameliorate inflammation in RA. Mechanistically, these metabolites influence immune cell differentiation, cytokine production, and gut barrier integrity, collectively shaping the autoimmune milieu. This review highlights recent advances in understanding the intricate crosstalk between microbiota metabolites and RA pathogenesis and also discusses the potential of specific metabolites to trigger or suppress autoimmunity, shedding light on their molecular interactions with immune cells and signaling pathways. Additionally, this review explores the translational aspects of microbiota metabolites as diagnostic and prognostic tools in RA. Furthermore, the challenges and prospects of translating these findings into clinical practice are critically examined.
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Affiliation(s)
- Zi-Feng Lu
- Heilongjiang Beidahuang Group General Hospital, Heilongjiang, China
| | - Chou-Yi Hsu
- Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | | | - Mohammed Ahmed Mustafa
- Department of Medical Laboratory Technology, University of Imam Jaafar AL-Sadiq, Kirkuk, Iraq
| | - Elena A Matveeva
- Department of Orthopaedic Dentistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
| | | | - Mohaned Adil
- Pharmacy College, Al-Farahidi University, Baghdad, Iraq
| | - Zainab H Athab
- Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
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32
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Zhang Z, Lv T, Wang X, Wu M, Zhang R, Yang X, Fu Y, Liu Z. Role of the microbiota-gut-heart axis between bile acids and cardiovascular disease. Biomed Pharmacother 2024; 174:116567. [PMID: 38583340 DOI: 10.1016/j.biopha.2024.116567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 04/01/2024] [Accepted: 04/04/2024] [Indexed: 04/09/2024] Open
Abstract
Bile acid (BA) receptors (e.g., farnesoid X-activated receptor, muscarinic receptor) are expressed in cardiomyocytes, endothelial cells, and vascular smooth muscle cells, indicating the relevance of BAs to cardiovascular disease (CVD). Hydrophobic BAs are cardiotoxic, while hydrophilic BAs are cardioprotective. For example, fetal cardiac insufficiency in maternal intrahepatic cholestasis during pregnancy, and the degree of fetal cardiac abnormality, is closely related to the level of hydrophobic BAs in maternal blood and infant blood. However, ursodeoxycholic acid (the most hydrophilic BA) can reverse/prevent these detrimental effects of increased levels of hydrophobic BAs on the heart. The gut microbiota (GM) and GM metabolites (especially secondary BAs) have crucial roles in hypertension, atherosclerosis, unstable angina, and heart failure. Herein, we describe the relationship between CVD and the GM at the BA level. We combine the concept of the "microbiota-gut-heart axis" (MGHA) and postulate the role and mechanism of BAs in CVD development. In addition, the strategies for treating CVD with BAs under the MGHA are proposed.
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Affiliation(s)
- Ziyi Zhang
- Department of Cardiovascular Medicine, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, PR China; Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China
| | - Tingting Lv
- Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China; Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, PR China
| | - Xiang Wang
- Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China
| | - Menglu Wu
- Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China
| | - Ruolin Zhang
- Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China
| | - Xiaopeng Yang
- Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China
| | - Yongping Fu
- Department of Cardiovascular Medicine, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang, PR China.
| | - Zheng Liu
- Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, PR China.
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33
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Ridlon JM, Gaskins HR. Another renaissance for bile acid gastrointestinal microbiology. Nat Rev Gastroenterol Hepatol 2024; 21:348-364. [PMID: 38383804 PMCID: PMC11558780 DOI: 10.1038/s41575-024-00896-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/16/2024] [Indexed: 02/23/2024]
Abstract
The field of bile acid microbiology in the gastrointestinal tract is going through a current rebirth after a peak of activity in the late 1970s and early 1980s. This renewed activity is a result of many factors, including the discovery near the turn of the century that bile acids are potent signalling molecules and technological advances in next-generation sequencing, computation, culturomics, gnotobiology, and metabolomics. We describe the current state of the field with particular emphasis on questions that have remained unanswered for many decades in both bile acid synthesis by the host and metabolism by the gut microbiota. Current knowledge of established enzymatic pathways, including bile salt hydrolase, hydroxysteroid dehydrogenases involved in the oxidation and epimerization of bile acid hydroxy groups, the Hylemon-Bjӧrkhem pathway of bile acid C7-dehydroxylation, and the formation of secondary allo-bile acids, is described. We cover aspects of bile acid conjugation and esterification as well as evidence for bile acid C3-dehydroxylation and C12-dehydroxylation that are less well understood but potentially critical for our understanding of bile acid metabolism in the human gut. The physiological consequences of bile acid metabolism for human health, important caveats and cautionary notes on experimental design and interpretation of data reflecting bile acid metabolism are also explored.
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Affiliation(s)
- Jason M Ridlon
- Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Center for Advanced Study, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Department of Microbiology & Immunology, Virginia Commonwealth University, Richmond, VA, USA.
| | - H Rex Gaskins
- Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Division of Nutritional Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Department of Biomedical and Translational Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
- Department of Pathobiology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
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34
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Cangiano LR, Villot C, Guan LL, Ipharraguerre IR, Steele MA. Graduate Student Literature Review: Developmental adaptations of immune function in calves and the influence of the intestinal microbiota in health and disease. J Dairy Sci 2024; 107:2543-2555. [PMID: 37939842 DOI: 10.3168/jds.2023-24195] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023]
Abstract
This graduate student literature review provides an examination of the ontological adaptations of the calf's immune system and how the intestinal microbiota influences calf immune function in health and disease. Within dairy rearing systems, various nutritional and management factors have emerged as critical determinants of development influencing multiple physiological axes in the calf. Furthermore, we discuss how multiple pre- and postnatal maternal factors influence the trajectory of immune development in favor of establishing regulatory networks to successfully cope with the new environment, while providing early immune protection via immune passive transfer from colostrum. Additionally, our review provides insights into the current understanding of how the intestinal microbiota contributes to the development of the intestinal and systemic immune system in calves. Lastly, we address potential concerns related to the use of prophylactic antimicrobials and waste milk, specifically examining their adverse effects on intestinal health and metabolic function. By examining these factors, we aim to better understand the intricate relationship between current management practices and their long-term effect on animal health.
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Affiliation(s)
- L R Cangiano
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706; Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON, Canada N1G 1Y2.
| | - C Villot
- Lallemand Animal Nutrition, F-31702 Blagnac, France, and Milwaukee, WI 53218
| | - L L Guan
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada, T6G 2P5
| | - I R Ipharraguerre
- Institute of Human Nutrition and Food Science, University of Kiel, D-24118 Kiel, Germany
| | - M A Steele
- Department of Animal Biosciences, Animal Science and Nutrition, University of Guelph, Guelph, ON, Canada N1G 1Y2
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Perdijk O, Azzoni R, Marsland BJ. The microbiome: an integral player in immune homeostasis and inflammation in the respiratory tract. Physiol Rev 2024; 104:835-879. [PMID: 38059886 DOI: 10.1152/physrev.00020.2023] [Citation(s) in RCA: 19] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 11/07/2023] [Accepted: 11/30/2023] [Indexed: 12/08/2023] Open
Abstract
The last decade of microbiome research has highlighted its fundamental role in systemic immune and metabolic homeostasis. The microbiome plays a prominent role during gestation and into early life, when maternal lifestyle factors shape immune development of the newborn. Breast milk further shapes gut colonization, supporting the development of tolerance to commensal bacteria and harmless antigens while preventing outgrowth of pathogens. Environmental microbial and lifestyle factors that disrupt this process can dysregulate immune homeostasis, predisposing infants to atopic disease and childhood asthma. In health, the low-biomass lung microbiome, together with inhaled environmental microbial constituents, establishes the immunological set point that is necessary to maintain pulmonary immune defense. However, in disease perturbations to immunological and physiological processes allow the upper respiratory tract to act as a reservoir of pathogenic bacteria, which can colonize the diseased lung and cause severe inflammation. Studying these host-microbe interactions in respiratory diseases holds great promise to stratify patients for suitable treatment regimens and biomarker discovery to predict disease progression. Preclinical studies show that commensal gut microbes are in a constant flux of cell division and death, releasing microbial constituents, metabolic by-products, and vesicles that shape the immune system and can protect against respiratory diseases. The next major advances may come from testing and utilizing these microbial factors for clinical benefit and exploiting the predictive power of the microbiome by employing multiomics analysis approaches.
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Affiliation(s)
- Olaf Perdijk
- Department of Immunology, School of Translational Science, Monash University, Melbourne, Victoria, Australia
| | - Rossana Azzoni
- Department of Immunology, School of Translational Science, Monash University, Melbourne, Victoria, Australia
| | - Benjamin J Marsland
- Department of Immunology, School of Translational Science, Monash University, Melbourne, Victoria, Australia
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36
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Chi L, YifeiYang, Bian X, Gao B, Tu P, Ru H, Lu K. Chronic sucralose consumption inhibits farnesoid X receptor signaling and perturbs lipid and cholesterol homeostasis in the mouse livers, potentially by altering gut microbiota functions. THE SCIENCE OF THE TOTAL ENVIRONMENT 2024; 919:169603. [PMID: 38272087 DOI: 10.1016/j.scitotenv.2023.169603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/27/2024]
Abstract
Sucralose has raised concerns regarding its safety and recent studies have demonstrated that sucralose consumption can disrupt the normal gut microbiome and alter metabolic profiles in mice. However, the extent to which this perturbation affects the functional interaction between the microbiota and the host, as well as its potential impact on host health, remains largely unexplored. Here, we aimed to investigate whether chronic sucralose consumption, at levels within the Acceptable Daily Intake (ADI), could disturb key gut microbial functions and lead to adverse health effects in mice. Following six-month sucralose consumption, several bacterial genera associated with bile acid metabolism were decreased, including Lactobacillus and Ruminococcus. Consequently, the richness of secondary bile acid biosynthetic pathway and bacterial bile salt hydrolase gene were decreased in the sucralose-treated gut microbiome. Compared to controls, sucralose-consuming mice exhibited significantly lower ratios of free bile acids and taurine-conjugated bile acids in their livers. Additionally, several farnesoid X receptor (FXR) agonists were decreased in sucralose-treated mice. This reduction in hepatic FXR activation was associated with altered expression of down-stream genes, in the liver. Moreover, the expression of key lipogenic genes was up-regulated in the livers of sucralose-treated mice. Changes in hepatic lipid profiles were also observed, characterized by lower ceramide levels, a decreased PC/PE ratio, and a mildly increase in lipid accumulation. Additionally, sucralose-consumed mice exhibited higher hepatic cholesterol level compared to control mice, with up-regulation of cholesterol efflux genes and down-regulation of genes associated with reverse cholesterol transport. In conclusion, chronic sucralose consumption disrupts FXR signaling activation and perturbs hepatic lipid and cholesterol homeostasis, potentially by diminishing the bile acid metabolic capacity of the gut microbiome. These findings shed light on the complex interplay between sucralose, the gut microbiota, and host metabolism, raising important questions about the safety of its long-term consumption.
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Affiliation(s)
- Liang Chi
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, United States
| | - YifeiYang
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, United States
| | - Xiaoming Bian
- Department of Environmental Health Sciences, University of Georgia, Athens, GA, 30602, United States of America
| | - Bei Gao
- Department of Environmental Health Sciences, University of Georgia, Athens, GA, 30602, United States of America
| | - Pengcheng Tu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, United States
| | - Hongyu Ru
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, United States
| | - Kun Lu
- Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599, United States; Institute for Environmental Health Solutions, University of North Carolina at Chapel Hill, NC 27599, United States.
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37
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Ping Y, Liu J, Wang L, Qiu H, Zhang Y. Research progress on the mechanism of TCM regulating intestinal microbiota in the treatment of DM mellitus. Front Endocrinol (Lausanne) 2024; 15:1308016. [PMID: 38601207 PMCID: PMC11004430 DOI: 10.3389/fendo.2024.1308016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Accepted: 03/12/2024] [Indexed: 04/12/2024] Open
Abstract
In recent years, with the improvement of people's living standards, the incidence of DM has increased year by year in China. DM is a common metabolic syndrome characterized by hyperglycemia caused by genetic, environmental and other factors. At the same time, long-term suffering from DM will also have an impact on the heart, blood vessels, eyes, kidneys and nerves, and associated serious diseases. The human body has a large and complex gut microbiota, which has a significant impact on the body's metabolism. Research shows that the occurrence and development of DM and its complications are closely related to intestinal microbiota. At present, western medicine generally treats DM with drugs. The hypoglycemic effect is fast and strong, but it can have a series of side effects on the human body. Compared with western medicine, Chinese medicine has its unique views and methods in treating DM. TCM can improve symptoms and treat complications by improving the imbalance of microbiota in patients with DM. Its characteristics of health, safety, and reliability are widely accepted by the general public. This article reviews the relationship between intestinal microbiota and DM, as well as the mechanism of TCM intervention in DM by regulating intestinal microbiota.
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Affiliation(s)
- Yang Ping
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
- Heilongjiang Pharmaceutical Research Institute, Jiamusi, Heilongjiang, China
| | - Jianing Liu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Lihong Wang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Hongbin Qiu
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
| | - Yu Zhang
- College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China
- Heilongjiang Pharmaceutical Research Institute, Jiamusi, Heilongjiang, China
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38
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Zhang L, Wang P, Huang J, Xing Y, Wong FS, Suo J, Wen L. Gut microbiota and therapy for obesity and type 2 diabetes. Front Endocrinol (Lausanne) 2024; 15:1333778. [PMID: 38596222 PMCID: PMC11002083 DOI: 10.3389/fendo.2024.1333778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 03/06/2024] [Indexed: 04/11/2024] Open
Abstract
There has been a major increase in Type 2 diabetes and obesity in many countries, and this will lead to a global public health crisis, which not only impacts on the quality of life of individuals well but also places a substantial burden on healthcare systems and economies. Obesity is linked to not only to type 2 diabetes but also cardiovascular diseases, musculoskeletal disorders, and certain cancers, also resulting in increased medical costs and diminished quality of life. A number of studies have linked changes in gut in obesity development. Dysbiosis, a deleterious change in gut microbiota composition, leads to altered intestinal permeability, associated with obesity and Type 2 diabetes. Many factors affect the homeostasis of gut microbiota, including diet, genetics, circadian rhythms, medication, probiotics, and antibiotics. In addition, bariatric surgery induces changes in gut microbiota that contributes to the metabolic benefits observed post-surgery. Current obesity management strategies encompass dietary interventions, exercise, pharmacotherapy, and bariatric surgery, with emerging treatments including microbiota-altering approaches showing promising efficacy. While pharmacotherapy has demonstrated significant advancements in recent years, bariatric surgery remains one of the most effective treatments for sustainable weight loss. However, access to this is generally limited to those living with severe obesity. This underscores the need for non-surgical interventions, particularly for adolescents and mildly obese patients. In this comprehensive review, we assess longitudinal alterations in gut microbiota composition and functionality resulting from the two currently most effective anti-obesity treatments: pharmacotherapy and bariatric surgery. Additionally, we highlight the functions of gut microbiota, focusing on specific bacteria, their metabolites, and strategies for modulating gut microbiota to prevent and treat obesity. This review aims to provide insights into the evolving landscape of obesity management and the potential of microbiota-based approaches in addressing this pressing global health challenge.
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Affiliation(s)
- Luyao Zhang
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
- Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| | - Pai Wang
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
- Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| | - Juan Huang
- Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, Changsha, Hunan, China
- Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yanpeng Xing
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
- Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
| | - F Susan Wong
- Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
| | - Jian Suo
- Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Li Wen
- Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, United States
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Németh K, Sterczer Á, Kiss DS, Lányi RK, Hemző V, Vámos K, Bartha T, Buzás A, Lányi K. Determination of Bile Acids in Canine Biological Samples: Diagnostic Significance. Metabolites 2024; 14:178. [PMID: 38668306 PMCID: PMC11052161 DOI: 10.3390/metabo14040178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/28/2024] Open
Abstract
The comprehensive examination of bile acids is of paramount importance across various fields of health sciences, influencing physiology, microbiology, internal medicine, and pharmacology. While enzymatic reaction-based photometric methods remain fundamental for total BA measurements, there is a burgeoning demand for more sophisticated techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) for comprehensive BA profiling. This evolution reflects a need for nuanced diagnostic assessments in clinical practice. In canines, a BA assessment involves considering factors, such as food composition, transit times, and breed-specific variations. Multiple matrices, including blood, feces, urine, liver tissue, and gallbladder bile, offer insights into BA profiles, yet interpretations remain complex, particularly in fecal analysis due to sampling challenges and breed-specific differences. Despite ongoing efforts, a consensus regarding optimal matrices and diagnostic thresholds remains elusive, highlighting the need for further research. Emphasizing the scarcity of systematic animal studies and underscoring the importance of ap-propriate sampling methodologies, our review advocates for targeted investigations into BA alterations in canine pathology, promising insights into pathomechanisms, early disease detection, and therapeutic avenues.
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Affiliation(s)
- Krisztián Németh
- Department of Physiology and Biochemistry, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary; (K.N.); (D.S.K.); (V.H.); (T.B.)
| | - Ágnes Sterczer
- Department of Internal Medicine, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary;
| | - Dávid Sándor Kiss
- Department of Physiology and Biochemistry, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary; (K.N.); (D.S.K.); (V.H.); (T.B.)
| | - Réka Katalin Lányi
- Faculty of Pharmacy, University of Szeged, Zrínyi u. 9, H-6720 Szeged, Hungary;
| | - Vivien Hemző
- Department of Physiology and Biochemistry, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary; (K.N.); (D.S.K.); (V.H.); (T.B.)
| | - Kriszta Vámos
- Department of Internal Medicine, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary;
| | - Tibor Bartha
- Department of Physiology and Biochemistry, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary; (K.N.); (D.S.K.); (V.H.); (T.B.)
| | - Anna Buzás
- Institute of Food Chain Science, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary; (A.B.); (K.L.)
| | - Katalin Lányi
- Institute of Food Chain Science, University of Veterinary Medicine, István u. 2, H-1078 Budapest, Hungary; (A.B.); (K.L.)
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40
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Dilmore AH, Kuplicki R, McDonald D, Kumar M, Estaki M, Youngblut N, Tyakht A, Ackermann G, Blach C, MahmoudianDehkordi S, Dunlop BW, Bhattacharyya S, Guinjoan S, Mandaviya P, Ley RE, Kaddaruh-Dauok R, Paulus MP, Knight R, Alzheimer Gut Microbiome Project Consortium. Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.03.19.585820. [PMID: 38562901 PMCID: PMC10983923 DOI: 10.1101/2024.03.19.585820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments are needed.
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Affiliation(s)
- Amanda Hazel Dilmore
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, California, USA
| | - Rayus Kuplicki
- Laureate Institute for Brain Research, Tulsa, Oklahoma, USA
| | - Daniel McDonald
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Megha Kumar
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Mehrbod Estaki
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Nicholas Youngblut
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Alexander Tyakht
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Gail Ackermann
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
| | - Colette Blach
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA
- Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Institute of Brain Sciences, Duke University, Durham, North Carolina, USA
| | | | - Boadie W. Dunlop
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | - Sudeepa Bhattacharyya
- Department of Biological Sciences, Arkansas Biosciences Institute, Arkansas State University, Jonesboro, AR, USA
| | | | - Pooja Mandaviya
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Ruth E. Ley
- Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany
| | - Rima Kaddaruh-Dauok
- Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, USA
- Department of Medicine, Duke University, Durham, North Carolina, USA
- Duke Institute of Brain Sciences, Duke University, Durham, North Carolina, USA
| | | | - Rob Knight
- Department of Pediatrics, University of California San Diego, La Jolla, California, USA
- Department of Computer Science & Engineering, University of California San Diego, La Jolla, California, USA
- Department of Bioengineering, University of California San Diego, La Jolla, California, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA
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Zeng F, Su X, Liang X, Liao M, Zhong H, Xu J, Gou W, Zhang X, Shen L, Zheng JS, Chen YM. Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults. BMC Med 2024; 22:104. [PMID: 38454425 PMCID: PMC10921631 DOI: 10.1186/s12916-024-03317-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 02/23/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD. METHODS The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites. RESULTS Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD. CONCLUSIONS We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.
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Affiliation(s)
- Fangfang Zeng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No.601 Huangpu Road West, Guangzhou, 510632, China.
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510275, China.
| | - Xin Su
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, No.601 Huangpu Road West, Guangzhou, 510632, China
| | - Xinxiu Liang
- Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Minqi Liao
- Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany
| | - Haili Zhong
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Jinjian Xu
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510275, China
| | - Wanglong Gou
- Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Xiangzhou Zhang
- Big Data Decision Institute, Jinan University, No.601 Huangpu Road West, Guangzhou, 510632, China
| | - Luqi Shen
- Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, 310030, China
| | - Ju-Sheng Zheng
- Zhejiang Key Laboratory of Multi-Omics in Infection and Immunity, School of Medicine and School of Life Sciences, Westlake University, Hangzhou, 310030, China.
| | - Yu-Ming Chen
- Department of Epidemiology, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, 510275, China.
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Fan C, He Y, Yang J, Da M. Association Between Live Microbe Intake and NAFLD: Evidence From NHANES 2003-2018. JOURNAL OF THE AMERICAN NUTRITION ASSOCIATION 2024; 43:272-278. [PMID: 37930261 DOI: 10.1080/27697061.2023.2270537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 10/10/2023] [Indexed: 11/07/2023]
Abstract
OBJECTIVE This study aimed to shed light on the potential relationship between live microbe intake and nonalcoholic fatty liver disease (NAFLD). METHOD By using a cross-sectional study design, the researchers were able to investigate the possible causal association between the two variables in a rigorous and systematic manner. RESULTS Our study investigated the correlation between the intake of live microbe-containing foods and NAFLD in a representative sample of adults. The study found that the intake of live microbe-containing foods was associated with lower blood pressure, plasma glucose, NAFLD, body mass index, glycated hemoglobin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and low-density lipoprotein cholesterol, as well as higher high-density lipoprotein cholesterol levels (p < 0.05). In univariate logistic regression, high dietary live microbe intake was associated with lower NAFLD prevalence than low intake (OR = 0.830; 95% CI, 0.759 to 0.908; p < 0.001). After adjusting for multiple variables, the same conclusion was supported (p < 0.05). In subgroup analyses, there was a significant difference in the race and smoking groups, with p for interaction of 0.01 and 0.02, respectively. This study's findings serve to augment the existing body of evidence linking live microbes with favorable health outcomes. CONCLUSIONS Our study revealed a robust correlation between dietary intake of live microbes and the prevalence of NAFLD in a cross-sectional analysis. Our findings offer a novel perspective on NAFLD research, highlighting the potential of targeted modulation of specific bacterial taxa, including the promotion of beneficial bacteria and suppression of harmful ones, as a promising strategy for preventing and treating NAFLD.
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Affiliation(s)
- Chuanlei Fan
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Yang He
- The First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
| | - Jian Yang
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Mingxu Da
- The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, China
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Apalowo OE, Adegoye GA, Obuotor TM. Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity. Curr Issues Mol Biol 2024; 46:1810-1831. [PMID: 38534735 DOI: 10.3390/cimb46030119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 03/28/2024] Open
Abstract
The increased prevalence of obesity with several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive diversity and complexities of the gut microbiota. Being recognized as a potential biomarker owing to its pivotal role in metabolic activities, the dysregulation of the gut microbiota can give rise to a persistent low-grade inflammatory state associated with chronic diseases during aging. This chronic inflammatory state, also known as inflammaging, induced by the chronic activation of the innate immune system via the macrophage, is controlled by the gut microbiota, which links nutrition, metabolism, and the innate immune response. Here, we present the functional roles of prebiotics, probiotics, synbiotics, and postbiotics as bioactive compounds by underscoring their putative contributions to (1) the reduction in gut hyperpermeability due to lipopolysaccharide (LPS) inactivation, (2) increased intestinal barrier function as a consequence of the upregulation of tight junction proteins, and (3) inhibition of proinflammatory pathways, overall leading to the alleviation of chronic inflammation in the management of obesity.
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Affiliation(s)
- Oladayo Emmanuel Apalowo
- Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Starkville, MS 39762, USA
| | - Grace Adeola Adegoye
- Department of Nutrition and Health Science, Ball State University, Muncie, IN 47306, USA
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Yang J, Pontoglio M, Terzi F. Bile Acids and Farnesoid X Receptor in Renal Pathophysiology. Nephron Clin Pract 2024; 148:618-630. [PMID: 38412845 DOI: 10.1159/000538038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/22/2024] [Indexed: 02/29/2024] Open
Abstract
BACKGROUND Bile acids (BAs) act not only as lipids and lipid-soluble vitamin detergents but also function as signaling molecules, participating in diverse physiological processes. The identification of BA receptors in organs beyond the enterohepatic system, such as the farnesoid X receptor (FXR), has initiated inquiries into their organ-specific functions. Among these organs, the kidney prominently expresses FXR. SUMMARY This review provides a comprehensive overview of various BA species identified in kidneys and delves into the roles of renal apical and basolateral BA transporters. Furthermore, we explore changes in BAs and their potential implications for various renal diseases, particularly chronic kidney disease. Lastly, we center our discussion on FXR, a key BA receptor in the kidney and a potential therapeutic target for renal diseases, providing current insights into the protective mechanisms associated with FXR agonist treatments. KEY MESSAGES Despite the relatively low concentrations of BAs in the kidney, their presence is noteworthy, with rodents and humans exhibiting distinct renal BA compositions. Renal BA transporters efficiently facilitate either reabsorption into systemic circulation or excretion into the urine. However, adaptive changes in BA transporters are evident during cholestasis. Various renal diseases are accompanied by alterations in BA concentrations and FXR expression. Consequently, the activation of FXR in the kidney could be a promising target for mitigating kidney damage.
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Affiliation(s)
- Jiufang Yang
- Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Université Paris Cité, Paris, France,
| | - Marco Pontoglio
- Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Université Paris Cité, Paris, France
| | - Fabiola Terzi
- Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Université Paris Cité, Paris, France
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Rodrigues SG, van der Merwe S, Krag A, Wiest R. Gut-liver axis: Pathophysiological concepts and medical perspective in chronic liver diseases. Semin Immunol 2024; 71:101859. [PMID: 38219459 DOI: 10.1016/j.smim.2023.101859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 10/11/2023] [Accepted: 12/04/2023] [Indexed: 01/16/2024]
Affiliation(s)
- Susana G Rodrigues
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Schalk van der Merwe
- Department of Gastroenterology and Hepatology, University hospital Gasthuisberg, University of Leuven, Belgium
| | - Aleksander Krag
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark, University of Southern Denmark, Odense, Denmark
| | - Reiner Wiest
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.
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Lejeune S, Kaushik A, Parsons ES, Chinthrajah S, Snyder M, Desai M, Manohar M, Prunicki M, Contrepois K, Gosset P, Deschildre A, Nadeau K. Untargeted metabolomic profiling in children identifies novel pathways in asthma and atopy. J Allergy Clin Immunol 2024; 153:418-434. [PMID: 38344970 DOI: 10.1016/j.jaci.2023.09.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 09/19/2023] [Accepted: 09/25/2023] [Indexed: 02/15/2024]
Abstract
BACKGROUND Asthma and other atopic disorders can present with varying clinical phenotypes marked by differential metabolomic manifestations and enriched biological pathways. OBJECTIVE We sought to identify these unique metabolomic profiles in atopy and asthma. METHODS We analyzed baseline nonfasted plasma samples from a large multisite pediatric population of 470 children aged <13 years from 3 different sites in the United States and France. Atopy positivity (At+) was defined as skin prick test result of ≥3 mm and/or specific IgE ≥ 0.35 IU/mL and/or total IgE ≥ 173 IU/mL. Asthma positivity (As+) was based on physician diagnosis. The cohort was divided into 4 groups of varying combinations of asthma and atopy, and 6 pairwise analyses were conducted to best assess the differential metabolomic profiles between groups. RESULTS Two hundred ten children were classified as At-As-, 42 as At+As-, 74 as At-As+, and 144 as At+As+. Untargeted global metabolomic profiles were generated through ultra-high-performance liquid chromatography-tandem mass spectroscopy. We applied 2 independent machine learning classifiers and short-listed 362 metabolites as discriminant features. Our analysis showed the most diverse metabolomic profile in the At+As+/At-As- comparison, followed by the At-As+/At-As- comparison, indicating that asthma is the most discriminant condition associated with metabolomic changes. At+As+ metabolomic profiles were characterized by higher levels of bile acids, sphingolipids, and phospholipids, and lower levels of polyamine, tryptophan, and gamma-glutamyl amino acids. CONCLUSION The At+As+ phenotype displays a distinct metabolomic profile suggesting underlying mechanisms such as modulation of host-pathogen and gut microbiota interactions, epigenetic changes in T-cell differentiation, and lower antioxidant properties of the airway epithelium.
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Affiliation(s)
- Stéphanie Lejeune
- Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; University of Lille, Pediatric Pulmonology and Allergy Department, Hôpital Jeanne de Flandre, CHU Lille, Lille, France; University of Lille, INSERM Unit 1019, CNRS UMR 9017, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
| | - Abhinav Kaushik
- Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Mass
| | - Ella S Parsons
- Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif
| | - Sharon Chinthrajah
- Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif
| | - Michael Snyder
- Department of Genetics, Stanford University School of Medicine, Stanford, Calif
| | - Manisha Desai
- Quantitative Science Unit, Department of Medicine, Stanford University School of Medicine, Stanford, Calif
| | - Monali Manohar
- Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif
| | - Mary Prunicki
- Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, Calif; Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Mass
| | - Kévin Contrepois
- Department of Genetics, Stanford University School of Medicine, Stanford, Calif
| | - Philippe Gosset
- University of Lille, INSERM Unit 1019, CNRS UMR 9017, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France
| | - Antoine Deschildre
- University of Lille, Pediatric Pulmonology and Allergy Department, Hôpital Jeanne de Flandre, CHU Lille, Lille, France; University of Lille, INSERM Unit 1019, CNRS UMR 9017, CHU Lille, Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France
| | - Kari Nadeau
- Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Mass
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Nie G, Zhang H, Xie D, Yan J, Li X. Liver cirrhosis and complications from the perspective of dysbiosis. Front Med (Lausanne) 2024; 10:1320015. [PMID: 38293307 PMCID: PMC10824916 DOI: 10.3389/fmed.2023.1320015] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Accepted: 12/26/2023] [Indexed: 02/01/2024] Open
Abstract
The gut-liver axis refers to the intimate relationship and rigorous interaction between the gut and the liver. The intestinal barrier's integrity is critical for maintaining liver homeostasis. The liver operates as a second firewall in this interaction, limiting the movement of potentially dangerous compounds from the gut and, as a result, contributing in barrier management. An increasing amount of evidence shows that increased intestinal permeability and subsequent bacterial translocation play a role in liver damage development. The major pathogenic causes in cirrhotic individuals include poor intestinal permeability, nutrition, and intestinal flora dysbiosis. Portal hypertension promotes intestinal permeability and bacterial translocation in advanced liver disease, increasing liver damage. Bacterial dysbiosis is closely related to the development of cirrhosis and its related complications. This article describes the potential mechanisms of dysbiosis in liver cirrhosis and related complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma, using dysbiosis of the intestinal flora as an entry point.
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Affiliation(s)
- Guole Nie
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Honglong Zhang
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Danna Xie
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Jun Yan
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China
- Cancer Prevention and Control Center of Lanzhou University Medical School, Lanzhou, China
- Gansu Institute of Hepatobiliary and Pancreatic Surgery, Lanzhou, China
- Gansu Clinical Medical Research Center of General Surgery, Lanzhou, China
| | - Xun Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
- Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China
- Cancer Prevention and Control Center of Lanzhou University Medical School, Lanzhou, China
- Gansu Institute of Hepatobiliary and Pancreatic Surgery, Lanzhou, China
- Gansu Clinical Medical Research Center of General Surgery, Lanzhou, China
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Zhou L, Lu G, Nie Y, Ren Y, Shi JS, Xue Y, Xu ZH, Geng Y. Restricted intake of sulfur-containing amino acids reversed the hepatic injury induced by excess Desulfovibrio through gut-liver axis. Gut Microbes 2024; 16:2370634. [PMID: 38935546 PMCID: PMC11212577 DOI: 10.1080/19490976.2024.2370634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 06/17/2024] [Indexed: 06/29/2024] Open
Abstract
Diet is a key player in gut-liver axis. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used rodent standard chow and purified diet to mimic two common human dietary patterns: grain and plant-based diet and refined-food-based diet, respectively and explored their impacts on gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in Desulfovibrio, gut bile acid (BA) levels elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation and elevated gut BA levels also occurred in mice fed with the chow diet after receiving Desulfovibrio desulfuricans ATCC 29,577 (DSV). Restriction of sulfur-containing amino acids (SAAs) prevented liver injury mainly through higher hepatic antioxidant and detoxifying ability and reversed the elevated BA levels due to excess Desulfovibrio. Ex vivo fermentation of human fecal microbiota with primary BAs demonstrated that DSV enhanced production of secondary BAs. Higher concentration of both primary and secondary BAs were found in the gut of germ-free mice after receiving DSV. In conclusion, Restriction of SAAs in diet may become an effective dietary intervention to prevent liver injury associated with excess Desulfovibrio in the gut.
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Affiliation(s)
- Lingxi Zhou
- The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China
| | - Gexue Lu
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China
| | - Yawen Nie
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China
| | - Yilin Ren
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Jin-Song Shi
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China
| | - Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Zheng-Hong Xu
- The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, Jiangsu, China
- College of Biomass Science and Engineering, Sichuan University, Chengdu, China
| | - Yan Geng
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, China
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
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Han L, Li Q, Du M, Mao X. Bovine milk osteopontin improved intestinal health of pregnant rats fed a high-fat diet through improving bile acid metabolism. J Dairy Sci 2024; 107:24-39. [PMID: 37690710 DOI: 10.3168/jds.2023-23802] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 07/31/2023] [Indexed: 09/12/2023]
Abstract
The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes, whereas it decreased Proteobacteria, Helicobacteraceae, and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis.
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Affiliation(s)
- Lihua Han
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Qiqi Li
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China
| | - Min Du
- Department of Animal Sciences, Washington State University, Pullman, WA 99163
| | - Xueying Mao
- Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
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Benedé-Ubieto R, Cubero FJ, Nevzorova YA. Breaking the barriers: the role of gut homeostasis in Metabolic-Associated Steatotic Liver Disease (MASLD). Gut Microbes 2024; 16:2331460. [PMID: 38512763 PMCID: PMC10962615 DOI: 10.1080/19490976.2024.2331460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 03/13/2024] [Indexed: 03/23/2024] Open
Abstract
Obesity, insulin resistance (IR), and the gut microbiome intricately interplay in Metabolic-associated Steatotic Liver Disease (MASLD), previously known as Non-Alcoholic Fatty Liver Disease (NAFLD), a growing health concern. The complex progression of MASLD extends beyond the liver, driven by "gut-liver axis," where diet, genetics, and gut-liver interactions influence disease development. The pathophysiology of MASLD involves excessive liver fat accumulation, hepatocyte dysfunction, inflammation, and fibrosis, with subsequent risk of hepatocellular carcinoma (HCC). The gut, a tripartite barrier, with mechanical, immune, and microbial components, engages in a constant communication with the liver. Recent evidence links dysbiosis and disrupted barriers to systemic inflammation and disease progression. Toll-like receptors (TLRs) mediate immunological crosstalk between the gut and liver, recognizing microbial structures and triggering immune responses. The "multiple hit model" of MASLD development involves factors like fat accumulation, insulin resistance, gut dysbiosis, and genetics/environmental elements disrupting the gut-liver axis, leading to impaired intestinal barrier function and increased gut permeability. Clinical management strategies encompass dietary interventions, physical exercise, pharmacotherapy targeting bile acid (BA) metabolism, and microbiome modulation approaches through prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT). This review underscores the complex interactions between diet, metabolism, microbiome, and their impact on MASLD pathophysiology and therapeutic prospects.
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Affiliation(s)
- Raquel Benedé-Ubieto
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
| | - Francisco Javier Cubero
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Yulia A. Nevzorova
- Department of Immunology, Ophthalmology and ENT, Complutense University School of Medicine, Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
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