Veränderte intestinale bakterielle Zusammensetzung bei Patienten mit Histaminintoleranz

Zusammenfassung

Hintergrund Die Existenz der Histaminintoleranz (HIT) ist umstritten. Als Ursache wird ein gestörter Histaminabbau infolge einer Diaminooxidase(DAO)-Defizienz vermutet. Doch auch andere Faktoren, z. B. eine erhöhte Histaminproduktion durch Darmbakterien, können zu erhöhten Histaminspiegel beitragen. Ziel dieser Untersuchung war es, eine mögliche Veränderung der Darmbakterien in histaminintoleranten Patienten im Vergleich zu gesunden Personen zu detektieren.

Material und Methodik Bei allen Studienprobanden erfolgte die Bestimmung von Gesamt-IgE, nahrungsmittelspezifischen IgEs, TNF-α, Plasmahistamin sowie der Serum-DAO-Aktivität. Anhand von Stuhlproben wurde die Histamin- und Zonulinkonzentration sowie die bakterielle Zusammensetzung mittels 16S-rRNA-Sequenzierung unter Verwendung der Illumina Plattform analysiert.

Ergebnisse Insgesamt 18 Probanden (30,2 ± 12,5 Jahre, 94,4 % weiblich) wurden in die Studie eingeschlossen. Diese umfassten Patienten mit HIT (n = 8; 28,9 ± 11,2 Jahre) und gesunde Kontrollen (n = 10; 31,3 ± 13,9 Jahre). Innerhalb der Studiengruppen wurden keine signifikanten Unterschiede in der Histaminkonzentration im Stuhl festgestellt, wohingegen die HIT-Patienten tendenziell erhöhte Zonulinkonzentration im Stuhl aufwiesen. Die Mikrobiomanalyse zeigte eine erniedrigte bakterielle α-Diversität (p = 0,05) und ein erhöhtes Vorkommen von Proteobacteria in der HIT-Gruppe. Weiterhin wiesen die HIT-Patienten ein signifikant geringeres Vorkommen der Butyrat-produzierenden Bakteriengattungen Faecalibacterium (p = 0,045) und Butyricimonas (p = 0,003) auf. Zudem waren die Anteile an Sutterella (p = 0,043) und Hespellia (p = 0,043) erniedrigt. In keiner Studiengruppe wurden vermehrt histaminproduzierende Bakterien detektiert.

Schlussfolgerung Unsere Ergebnisse deuten auf eine veränderte Darm-Mikrobiota in Patienten mit HIT hin. Der erhöhte Anteil von Proteobacteria und der erniedrigte Anteil an Butyrat-produzierenden Bakterien sowie höhere Zonulinwerte im Stuhl weisen dabei auf eine mögliche Dysbiose oder eine gestörte Darmbarriere hin. Eine erhöhte intestinale Histaminexposition durch Darmbakterien scheint in der Pathogenese der Histaminintoleranz hingegen unwahrscheinlich.

Abstract

Background Histamine intolerance (HIT) is a controversially discussed disorder. An impaired degradation of oral histamine intake due to diamine oxidase (DAO) deficiency is suggested as main cause, but other factors, including an altered gut flora, may also contribute to elevated histamine levels. We aimed to determine differences in the intestinal bacterial pattern of HIT-patients in comparison to healthy persons (HC).

Material and methods All participants had a blood testing for total IgE, food-specific IgEs, TNF-α, plasma histamine and serum DAO activities. Stool samples were collected for analysis of stool histamine and zonulin levels. The bacterial composition of the stool samples was analysed by 16 s rRNA sequencing using Illumina platform.

Results A total of 18 participants (30.2 ± 12.5 yrs, 94,4 % female) were included in the study, and categorized into HIT-patients (n = 8, 28.9 ± 11.2 yrs, 100 % female) and healthy controls (n = 10, 31.3 ± 13.9 yrs, 90 % female). No significant differences in stool histamine levels were observed between groups, but HIT-patients showed tendentially increased levels of fecal zonulin. Microbiome analysis revealed a reduced bacterial diversity (p = 0.05) and a higher abundance of Proteobacteria in the HIT-group. Additionally, HIT-patients showed a significantly decreased abundance of the butyrate-producing genera Faecalibacterium (p = 0.045) and Butyricimonas (p = 0.003) as well as lower proportions of Sutterella (p = 0.043) and Hespellia (p = 0.043). No increased numbers of known histamine-producing bacteria were detected in the study groups.

Conclusion Our study results suggest an alteration of the microbial composition in HIT-patients. The higher abundance of Proteobacteria and lower abundance of butyrate-producing bacteria, as well as elevated stool zonulin levels indicate a dysbiosis and impaired intestinal barrier. However, an elevated histamine exposure due to gut bacteria may not be responsible for HIT pathogenesis.

Schlüsselwörter

Histaminintoleranz - Dysbiose - Mikrobiom - Darmbarriere

Keywords

histamine intolerance - dysbiosis - microbiome - intestinal barrier

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