{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:17:56Z","timestamp":1787807876626,"version":"build-2784847793"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pathogenesis of brucellar spondylitis (BLS) has traditionally been considered to be primarily limited to local osteoarticular lesions. With the proposal of the \u201cgut-spine axis\u201d concept, the role of intestinal microecological dysbiosis in inflammatory spinal diseases has attracted in an increase of attention. The overactivated inflammatory cytokine network not only mediates bone destruction and intervertebral disc damage, but also forms a bidirectional interaction with gut microbiota dysbiosis through the \u201cgut-spine axis,\u201d collectively driving disease progression. However, the inflammatory mechanism by which gut microbiota participates in the pathological process of BLS remains largely unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study recruited 20 BLS patients and 20 healthy donors. Multi-omics analysis including metagenomics, untargeted metabolomics, and targeted short-chain fatty acids (SCFAs) analysis, were used to compare the structural differences in gut microbiota between the two groups and screen for signature differential bacterial species. Plasma levels of histamine and histidine decarboxylase were measured by ELISA to clarify the role of differential histidine metabolic pathway in the disease. Additionally, plasma levels of lipopolysaccharide (LPS) and inflammatory cytokines (IL-1\u03b2, IL-6, IL-10, IL-17A, TNF-\u03b1) were detected by ELISA. The correlation between gut microbiota and inflammatory indicators was further analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to the healthy control group, the \u03b1-diversity of the gut microbiota in BLS patients was significantly reduced, with the microbial community structure exhibiting increased homogeneity. Beta diversity analysis revealed significant differences, suggesting that disease progression is associated with an overall imbalance in the gut microbiota and the deterioration of its specific structural composition. At the phylum level, the abundances of\n                      <jats:italic>Actinomycetota<\/jats:italic>\n                      ,\n                      <jats:italic>unclassified_d_Viruses<\/jats:italic>\n                      , and\n                      <jats:italic>Fusobacteriota<\/jats:italic>\n                      were significantly increased in the gut microbiota of BLS patients compared to the control group, while the abundances of\n                      <jats:italic>Bacillota<\/jats:italic>\n                      and\n                      <jats:italic>Pseudomonadota<\/jats:italic>\n                      were significantly decreased. Further analysis revealed that, compared to the control group, the generic abundance of\n                      <jats:italic>Enterococcus<\/jats:italic>\n                      was significantly increased, while the proportions of\n                      <jats:italic>Blautia, Faecalibacterium, Ruminococcus, Agathobacter, Roseburia, Clostridium, Eubacterium, Alistipes<\/jats:italic>\n                      and\n                      <jats:italic>Anaerobutyricum<\/jats:italic>\n                      were significantly decreased. At the species level, the abundances of\n                      <jats:italic>Enterococcus sp<\/jats:italic>\n                      and\n                      <jats:italic>Enterococcus-faecium<\/jats:italic>\n                      were increased, whereas\n                      <jats:italic>Blautia sp, Ruminococcus sp, Faecalibacterium sp, Faecalibacterium prausnitzii, Agathobacter rectalis, Eubacterium sp, Agathobacter sp<\/jats:italic>\n                      , and\n                      <jats:italic>Roseburia<\/jats:italic>\n                      sp were decreased. Furthermore, untargeted metabolomics revealed that metabolites were enriched in the histidine metabolic pathway, and the levels of SCFAs including butyrate, isobutyrate, valerate, and 4-methylvalerate in the intestinal contents were reduced in BLS. Functional KEGG profiling revealed that key KOs involved in butyrate synthesis (e.g., K00074, K00172, K01640) and transport were globally downregulated in the patient group, whereas histidine decarboxylase KOs (K01693, K11755, K19787) that convert histidine to pro-inflammatory histamine were significantly enriched. The loss of butyrate-producing symbionts led to SCFAs deficiency and mucosal barrier disruption, creating ecological niches for facultatively anaerobic Enterococcus, which further exacerbated local inflammation via proteolytic fermentation and histamine production. Compared with the control group, BLS patients showed decreased plasma levels of IL-10, while levels of IL-1\u03b2, IL-6, IL-17A, and TNF-\u03b1 were increased, and LPS levels were elevated. In addition, significantly elevated plasma pro-inflammatory LPS levels in patients with BLS suggest disruption of intestinal integrity and permeability. Correlation analysis indicated a close relationship between gut microbiota and inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BLS is associated with gut microbiota dysbiosis and alterations in microbial metabolites, which may be linked to inflammatory responses and histamine metabolism. The differential microbial taxa identified in this study could be developed into a stool-based non-invasive diagnostic panel to facilitate early differentiation of BLS from other spinal disorders. Furthermore, restoring gut microbial balance through probiotic supplementation or dietary modulation may represent a promising adjunctive strategy to enhance the efficacy of standard antibiotic therapy and reduce disease recurrence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1914654","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:27:07Z","timestamp":1787804827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Brucellar spondylitis is associated with disturbance in gut microbiota and histamine metabolism associated inflammation"],"prefix":"10.3389","volume":"16","author":[{"given":"Zongjun","family":"Ma","sequence":"first","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]},{"name":"The First Clinical College, General Hospital, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Bai","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Fourth People's Hospital of Ningxia Hui Autonomous Region","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenfei","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Fourth People's Hospital of Ningxia Hui Autonomous Region","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijia","family":"Yan","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Ma","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cunlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbai","family":"Ma","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Infection and Immunity, School of Basic Medical Sciences, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B34","first-page":"113","article-title":"Mechanism of lncRNA GSEC in promoting macrophage polarization via regulating CTCF in BLS","volume":"29","author":"Aribenjirigala","year":"2025","journal-title":"J. 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