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. 2024 Jul 11:15:1390483.
doi: 10.3389/fphar.2024.1390483. eCollection 2024.

Global research trends on gut microbiota and metabolic dysfunction-associated steatohepatitis: Insights from bibliometric and scientometric analysis

Naqash Alam  1 , Linying Jia  1 , Ao Cheng  1 , Honghao Ren  1 , Yu Fu  1 , Xinhua Ding  1 , Ihtisham Ul Haq  2 , Enqi Liu  1
Affiliations

Global research trends on gut microbiota and metabolic dysfunction-associated steatohepatitis: Insights from bibliometric and scientometric analysis

Naqash Alam et al. Front Pharmacol. .

Abstract

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is an inflammatory subtype of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD, a common, multifactorial and poorly understood liver disease whose incidence is increasing worldwide. In recent years, there has been increasing scientific interest in exploring the relationship between gut microbiota and MASH. To learn more about the gut microbiota in MASH, this study aims to provide a comprehensive analysis of the knowledge structure and research hotspots from a bibliometric perspective.

Methods: We searched the Web of Science Core Collection for articles and reviews that covered the connections between gut microbiota and MASH over the last decade. The Online Analysis Platforms, VOSviewer, CiteSpace, the R tool "bibliometrix" were used to analyzed existing publications trends and hotspots.

Results: A total of 4,069 documents related to the interaction between gut microbiota and MASH were retrieved from 2014 to 2023. The number of annual publications increased significantly over the last decade, particularly in the United States and China. The University of California-San Diego was the most productive institution, while researcher Rohit Loomba published the most papers in the field. Younossi ZM was ranked as the first co-cited author and largest contributor of highly cited articles in the field. Gastroenterology and hepatology were the most common specialty category. The most cited journal in the last decade was Hepatology. The Keyword Bursts analysis highlighted the importance of studying the association between gut microbiota and MASH, as well as related factors such as metabolic syndrome, insulin resistance, endotoxemia and overgrowth of gut bacteria. Keyword clusters with co-citation were used to illustrate important topics including intestinal permeability, insulin sensitivity and liver immunology. The most common keywords include insulin resistance, obesity, dysbiosis, inflammation and oxidative stress, which are current hotspots.

Conclusion: Our analysis highlights key aspects of this field and emphasizes multiorgan crosstalk in MASLD/MASH pathogenesis. In particular, the central role of the gut-liver axis and the significant influence of gut microbiota dysbiosis on disease progression are highlighted. Furthermore, our results highlight the transformative potential of microbiota-specific therapies and cover the way for innovative healthcare and pharmaceutical strategies.

Keywords: Citespace; NASH; VOSviewer; bibliometrix; gut microbiota; visualization.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of the search and selection process, including the criteria for inclusion and exclusion of publications.
FIGURE 2
FIGURE 2
Analysis of publications on the associations between gut microbiota and MASH from 2014 to 2023. (A) Annual research publications and growth patterns on gut microbiota and MASH, data exported from WoSCC. (B) Annual research publications and growth trends on gut microbiota and MASH, data exported from an online literature metrology analysis platform. (C) Top 10 countries by total number of citations. (D) Top 10 research areas by number of publications.
FIGURE 3
FIGURE 3
(A) Collaborative relationships 97 countries/regions studying gut microbiota and MASH from 2014 to 2023, analyzed using an online literature metrology platform. (B) VOSviewer network map of the top 100 most productive institutions in gut microbiota and MASH research. Cluster size reflects the number of publications, while line thickness indicates the degree of inter-institutional collaboration.
FIGURE 4
FIGURE 4
VOSviewer network analysis of authorship and co-citation in gut microbiota and MASH research. (A) Overlay visualization of authors. (B) Density visualization of co-cited authors. Each circle represents an author, with connections indicating collaboration. Font size correlates with the number of published articles. (C) Citation network and clusters of the top 100 most cited journals. (D) Network visualization of the most cited journals based on VOSviewer analysis.
FIGURE 5
FIGURE 5
(A) Dual-map overlay of journals related to gut microbiota and MASH generated by CiteSpace. (B) CiteSpace-generated clustered networks showing co-citation relationships between the investigated references and the 4,069 citing articles.
FIGURE 6
FIGURE 6
(A) Co-citation map of 119,803 references connections in gut microbiota and MASH research, with the filter option showing only the largest connected component. (B) Clustering analysis of high-frequency keywords. (C) Word cloud illustrates the top 100 most frequently used terms in studies exploring the relationship between gut microbiota and MASH. (Panel A and C generated using R package Bibloshiny, while Panel B was created using VOSviewer).
FIGURE 7
FIGURE 7
(A) Analysis of the reference with the highest burst strength among 4,069 citing articles on gut microbiota and MASH research published from 2014 to 2023. References marked in red denote a significant increase in usage frequency during this period, while blue indicates a comparatively lower frequency. (B) Keywords with the highest burst strength. Keywords highlighted in red denote a notable increase in usage, while blue denotes a less prominent period of usage. (The figure created using CiteSpace).
FIGURE 8
FIGURE 8
(A) A three-field plot (Sankey diagram) illustrates prolific authors, their countries and areas of interest represented by keywords in the field of gut microbiota and MASH research. (B) Thematic evolution across three phases of gut microbiota and MASH research, depicted by lines connecting nodes that reflect the evolving focus of the research topic. Line width indicates the number of common keywords, with thicker lines indicating greater thematic importance. (Figure generated using R package Bibloshiny).
FIGURE 9
FIGURE 9
The role of FXR in maintaining BAs and metabolic homeostasis in MASH. BAs synthesized from cholesterol in the liver are excreted into bile via BSEP. Enterocytes mediate BA uptake and export into portal blood via ASBT and OSTα/β, respectively, with hepatocellular reuptake via NTCP completing the enterohepatic circulation. FXR activation increases bile secretion via BSEP and reduces BA synthesis and uptake via NTCP, thereby maintaining BA homeostasis. In MASH, hepatic FXR activation promotes FA oxidation, reduces de novo lipogenesis, inhibits inflammation (via NF-κB, NLRP3, and CCL-2), and reduces fibrosis (via TGF-β1 and ECM deposition by HSCs). FXR also upregulates FGF21, reduces cholesterol and triglyceride synthesis, lowers glucose levels, and increases adiponectin and adipocyte browning. FXR activation in the intestine increases FGF15/19, which binds to FGFR4/β-Klotho, increases fatty acid oxidation and glycogen synthesis, and inhibits CYP7A1 to reduce BA synthesis. Furthermore, FXR activation maintains the integrity of the intestinal barrier, prevents bacterial translocation, induces antibacterial peptides, and restores intestinal microbiota balance. FXR, farnesoid X receptor; BA, bile acid; BSEP, bile salt export pump; ASBT, apical sodium-dependent bile acid transporter; OSTα/β, organic solute transporter-α/β; NTCP, sodium taurocholate cotransporting polypeptide; NF-κB, nuclear factor j-light-chain enhancer of activated B cells; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; CCL-2, C–C motif chemokine ligand 2; TGF-β1, transforming growth factor-β1; ECM, extracellular matrix; HSC, hepatic stellate cell; FA, fatty acid; PEPCK, phosphoenolpyruvate carboxykinase; SREBP-1c, sterol regulatory element factor binding protein-1c; TG, triglyceride; FGF, fibroblast growth factor; SHP, small heterodimer partner. (Figure created with BioRender).
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References

    1. Adolph T. E., Grander C., Moschen A. R., Tilg H. (2018). Liver-microbiome Axis in health and disease. Trends Immunol. 39 (9), 712–723. 10.1016/j.it.2018.05.002 - DOI - PubMed
    1. Agirman G., Hsiao E. Y. (2021). SnapShot: the microbiota-gut-brain axis. Cell 184 (9), 2524–2524.e1. 10.1016/j.cell.2021.03.022 - DOI - PubMed
    1. Albillos A., de Gottardi A., Rescigno M. (2020). The gut-liver axis in liver disease: pathophysiological basis for therapy. J. Hepatol. 72 (3), 558–577. 10.1016/j.jhep.2019.10.003 - DOI - PubMed
    1. Angulo P., Kleiner D. E., Dam-Larsen S., Adams L. A., Bjornsson E. S., Charatcharoenwitthaya P., et al. (2015). Liver fibrosis, but No other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology 149 (2), 389–397. 10.1053/j.gastro.2015.04.043 - DOI - PMC - PubMed
    1. Aoki R., Onuki M., Hattori K., Ito M., Yamada T., Kamikado K., et al. (2021). Commensal microbe-derived acetate suppresses NAFLD/NASH development via hepatic FFAR2 signalling in mice. Microbiome 9 (1), 188. 10.1186/s40168-021-01125-7 - DOI - PMC - PubMed

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