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Background <p>Immunogenicity to influenza vaccination is often impaired in systemic lupus erythematosus (SLE). The role of the gut microbiota and its metabolic output in modulating this response remains underexplored. This study is the first to explore gut microbiota patterns and metabolites in response to influenza vaccination in patients with SLE.</p> Methods <p>A cross-sectional observational pilot study was conducted at Ramathibodi Hospital between May 2021 and July 2022. Participants with SLE who had received either a boosted dose or a standard dose of a quadrivalent influenza vaccine were enrolled. We analyzed fecal 16&#xa0;S rDNA and metabolomic profiles using liquid chromatography–mass spectrometry to identify signatures associated with seroconversion (determined using the hemagglutination inhibition assay).</p> Results <p>A total of 62 participants with SLE participated in the study, and 61 fecal samples were submitted for metabolomic analysis. Most participants were female (58/62, 93.6%). The median ages in the standard and booster dose groups were 35.5 (interquartile range 28–42.5) and 34 (25–43) years, respectively (<i>P</i> = 0.878). The overall gut microbiota patterns were similar in both groups; however, the genus <i>Bacteroides</i> was significantly associated with seroconversion to A(H1N1) and A(H3N2) (<i>P</i> &lt; 0.05). Metabolomic analysis identified upregulation of 1,5-anhydro-D-glucitol and L-cysteic acid in seroconverters, whereas neopterin was significantly elevated in nonresponders, furthermore, several bacterial taxa were correlated with these metabolites. The level of immunosuppressive treatment and the use of antimicrobials for prophylaxis against opportunistic infections affected influenza immunogenicity in this study population. Some metabolites also appeared to be linked to vaccine immunogenicity, although the underlying mechanism is unclear.</p> Conclusions <p>Our findings identify specific gut microbial taxa and fecal metabolites, particularly 1,5-anhydro-D-glucitol, which are significantly associated with influenza vaccine immunogenicity in SLE patients. These results suggest that the gut–immune axis may play a modulatory role in vaccine responses and may provide potential non-invasive biomarkers that can identify patients at risk of suboptimal influenza protection.</p>

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Patterns of the gut microbiota and metabolome as potential biomarkers associated with influenza vaccine immunogenicity in systemic lupus erythematosus: a cross-sectional observational pilot study

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  • 发表日期：

    2026年7月31日

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  • Nathathai Kiewsanuan,
  • Pintip Ngamjanyaporn,
  • Prapaporn Pisitkun,
  • Sunchai Payungporn,
  • Vorthon Sawaswong,
  • Prangwalai Chanchaem,
  • Arnatchai Maiuthed,
  • Supranee Thongpradit,
  • Napong Lohaphuntrakun,
  • Pichakorn Juntranggoor,
  • Porpon Rotjanapan

摘要

Background

Immunogenicity to influenza vaccination is often impaired in systemic lupus erythematosus (SLE). The role of the gut microbiota and its metabolic output in modulating this response remains underexplored. This study is the first to explore gut microbiota patterns and metabolites in response to influenza vaccination in patients with SLE.

Methods

A cross-sectional observational pilot study was conducted at Ramathibodi Hospital between May 2021 and July 2022. Participants with SLE who had received either a boosted dose or a standard dose of a quadrivalent influenza vaccine were enrolled. We analyzed fecal 16 S rDNA and metabolomic profiles using liquid chromatography–mass spectrometry to identify signatures associated with seroconversion (determined using the hemagglutination inhibition assay).

Results

A total of 62 participants with SLE participated in the study, and 61 fecal samples were submitted for metabolomic analysis. Most participants were female (58/62, 93.6%). The median ages in the standard and booster dose groups were 35.5 (interquartile range 28–42.5) and 34 (25–43) years, respectively (P = 0.878). The overall gut microbiota patterns were similar in both groups; however, the genus Bacteroides was significantly associated with seroconversion to A(H1N1) and A(H3N2) (P < 0.05). Metabolomic analysis identified upregulation of 1,5-anhydro-D-glucitol and L-cysteic acid in seroconverters, whereas neopterin was significantly elevated in nonresponders, furthermore, several bacterial taxa were correlated with these metabolites. The level of immunosuppressive treatment and the use of antimicrobials for prophylaxis against opportunistic infections affected influenza immunogenicity in this study population. Some metabolites also appeared to be linked to vaccine immunogenicity, although the underlying mechanism is unclear.

Conclusions

Our findings identify specific gut microbial taxa and fecal metabolites, particularly 1,5-anhydro-D-glucitol, which are significantly associated with influenza vaccine immunogenicity in SLE patients. These results suggest that the gut–immune axis may play a modulatory role in vaccine responses and may provide potential non-invasive biomarkers that can identify patients at risk of suboptimal influenza protection.