Gut Microbiome

Brucellar spondylitis is associated with disturbance in gut microbiota and histamine metabolism associated inflammation.

TL;DR

BLS is associated with gut microbiota dysbiosis and alterations in microbial metabolites, which may be linked to inflammatory responses and histamine metabolism.

Key Findings

Alpha diversity of gut microbiota was significantly reduced in brucellar spondylitis patients compared to healthy controls, with increased microbial community homogeneity.

  • 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
  • Beta diversity analysis revealed significant differences in microbial community structure between groups
  • Disease progression was associated with an overall imbalance in gut microbiota and deterioration of its specific structural composition

At the phylum level, abundances of Actinomycetota, unclassified_d_Viruses, and Fusobacteriota were significantly increased in BLS patients, while Bacillota and Pseudomonadota were significantly decreased.

  • Comparison was made between 20 BLS patients and 20 healthy controls
  • Metagenomics was the analytical method used for microbial community profiling
  • Both increases and decreases in specific phyla were observed, indicating bidirectional dysbiosis
  • These phylum-level changes reflected an overall restructuring of the gut microbial ecosystem in BLS

At the genus level, Enterococcus abundance was significantly increased in BLS patients, while multiple butyrate-producing genera were significantly decreased.

  • Genera significantly decreased included Blautia, Faecalibacterium, Ruminococcus, Agathobacter, Roseburia, Clostridium, Eubacterium, Alistipes, and Anaerobutyricum
  • At the species level, Enterococcus sp and Enterococcus faecium were increased
  • Decreased species included Blautia sp, Ruminococcus sp, Faecalibacterium sp, Faecalibacterium prausnitzii, Agathobacter rectalis, Eubacterium sp, Agathobacter sp, and Roseburia sp
  • Loss of butyrate-producing symbionts was proposed to create ecological niches for facultatively anaerobic Enterococcus

Intestinal levels of short-chain fatty acids including butyrate, isobutyrate, valerate, and 4-methylvalerate were reduced in BLS patients.

  • Targeted SCFAs analysis was used to measure intestinal content metabolite levels
  • 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
  • SCFAs deficiency was associated with mucosal barrier disruption in BLS
  • The reduction in butyrate-producing bacteria was mechanistically linked to the observed SCFAs deficiency

Untargeted metabolomics revealed enrichment of metabolites in the histidine metabolic pathway, and histidine decarboxylase KOs were significantly enriched in BLS patients.

  • Histidine decarboxylase KOs identified as enriched included K01693, K11755, and K19787
  • These KOs convert histidine to pro-inflammatory histamine
  • Plasma levels of histamine and histidine decarboxylase were measured by ELISA to clarify the role of the differential histidine metabolic pathway
  • Enterococcus was proposed to exacerbate local inflammation via proteolytic fermentation and histamine production

BLS patients showed an altered inflammatory cytokine profile, with decreased IL-10 and increased IL-1β, IL-6, IL-17A, and TNF-α compared to healthy controls.

  • Plasma cytokine levels were measured by ELISA
  • Anti-inflammatory cytokine IL-10 was decreased in BLS patients
  • Pro-inflammatory cytokines IL-1β, IL-6, IL-17A, and TNF-α were all increased in BLS patients
  • LPS levels were also elevated in BLS patients, suggesting disruption of intestinal integrity and permeability

Plasma LPS levels were significantly elevated in BLS patients, indicating disruption of intestinal integrity and increased intestinal permeability.

  • LPS levels were measured by ELISA in plasma samples
  • Elevated LPS was interpreted as evidence of mucosal barrier disruption
  • Correlation analysis indicated a close relationship between gut microbiota composition and inflammatory indicators including LPS
  • SCFAs deficiency and mucosal barrier disruption were proposed as mechanisms linking gut dysbiosis to elevated systemic LPS

Correlation analysis demonstrated a close relationship between gut microbiota composition and inflammatory indicators in BLS patients.

  • Correlation analysis was performed between gut microbiota metrics and inflammatory indicators
  • The overactivated inflammatory cytokine network was proposed to mediate bone destruction and intervertebral disc damage
  • A bidirectional interaction between gut microbiota dysbiosis and inflammatory cytokine networks through the 'gut-spine axis' was suggested
  • The findings collectively support the role of intestinal microecological dysbiosis in BLS pathogenesis

What This Means

This research suggests that brucellar spondylitis (BLS), a serious spinal infection caused by the Brucella bacterium, is not just a local bone and joint problem but is also associated with significant disruptions in the gut microbiome. Researchers compared the gut bacteria, metabolites, and blood inflammatory markers of 20 BLS patients with 20 healthy individuals. They found that BLS patients had less diverse gut bacteria overall, with notable losses of beneficial bacteria (particularly those that produce short-chain fatty acids like butyrate) and increases in potentially harmful bacteria like Enterococcus. These changes were accompanied by lower levels of protective gut metabolites and higher levels of inflammatory molecules in the blood, including elevated LPS—a bacterial product that signals a leaky gut barrier. A particularly notable finding was that metabolic pathways related to histamine production appeared to be more active in BLS patients. The enrichment of histidine decarboxylase genes—enzymes that convert the amino acid histidine into pro-inflammatory histamine—suggests that gut bacteria in BLS patients may be fueling inflammation through histamine production. At the same time, the loss of butyrate-producing bacteria appeared to weaken the gut lining, potentially allowing bacterial products like LPS to enter the bloodstream and trigger systemic inflammation. The pattern of inflammatory cytokines in the blood (higher IL-1β, IL-6, IL-17A, TNF-α, and lower IL-10) was consistent with an overactive inflammatory state. This research suggests that the gut microbiome plays a meaningful role in BLS disease progression through what the authors call the 'gut-spine axis.' The distinct patterns of gut bacteria found in BLS patients could potentially be developed into a non-invasive stool-based diagnostic tool to help distinguish BLS from other spinal conditions. Additionally, interventions aimed at restoring healthy gut bacteria—such as probiotic supplementation or dietary changes—might represent a promising complementary approach alongside standard antibiotic treatment to improve outcomes and reduce disease recurrence.

Have a question about this study?

Citation

Ma Z, Bai X, Tian J, Yao C, Yan Z, Ma X, et al.. (2026). Brucellar spondylitis is associated with disturbance in gut microbiota and histamine metabolism associated inflammation.. Frontiers in cellular and infection microbiology. https://doi.org/10.3389/fcimb.2026.1914654