小児リウマチ発症の何年も前に腸内細菌叢が乱れていた(Disrupted gutflora observed many years before onset of child rheumatism)

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2023-07-05 リンショーピング大学

◆小児リウマチは子供の間で最も一般的な関節炎の炎症性疾患であり、免疫系を抑制する医薬品によって治療されています。この自己免疫疾患は、免疫系が体内の組織を攻撃し、関節などの炎症を引き起こすことを意味します。免疫系がなぜこのような反応を起こすのかはまだ分かっていません。腸内細菌の種類と量は免疫系の発達に大きな影響を与えます。
◆本研究では、リウマチの発症前の数年間にわたって腸内細菌を調査し、特定の菌の存在がリウマチのリスクと関連していることが明らかになりました。また、母乳育児は疾患のリスクを減少させることも示されました。今後は、特定の菌に対するターゲット治療や腸の健康改善など、個別化された介入策の開発につながる可能性があります。

<関連情報>

乳幼児期の腸内細菌叢と環境が、若年性特発性関節炎と発症の何年も前から、特に遺伝的に脆弱な小児において関連している。 Infant gut microbiota and environment associate with juvenile idiopathic arthritis many years prior to disease onset, especially in genetically vulnerable children

Erik Kindgren,Angelica P. Ahrens,Eric W. Triplett,Johnny Ludvigsson
eBioMedicine  Published:June 14, 2023
DOI:https://doi.org/10.1016/j.ebiom.2023.104654

小児リウマチ発症の何年も前に腸内細菌叢が乱れていた(Disrupted gutflora observed many years before onset of child rheumatism)

Summary

Background
The etiology of juvenile idiopathic arthritis (JIA) is poorly understood. This study investigated genetic and environmental factors and infant gut microbiota in a prospective birth cohort to assess disease risk.

Methods
Data was collected from the All Babies in Southeast Sweden (ABIS) population-based cohort (n = 17,055), 111 of whom later acquired JIA (ABISJIA). Stool samples were collected at one year of age for 10.4%. To determine disease association, 16S rRNA gene sequences were analyzed, with and without confound adjustment. Genetic and environmental risks were assessed.

Findings
ABISJIA had higher abundance of Acidaminococcales, Prevotella 9, and Veillonella parvula and lower abundance of Coprococcus, Subdoligranulum, Phascolarctobacterium, Dialister spp., Bifidobacterium breve, Fusicatenibacter saccharivorans, Roseburia intestinalis, and Akkermansia muciniphila (q’s < 0.05). Parabacteroides distasonis greatly increased the odds of later contracting JIA (OR = 6.7; 1.81–24.84, p = 0.0045). Shorter breastfeeding duration and increased antibiotic exposure compounded risk in a dose-dependent manner, especially in those with genetic predisposition.

Interpretation
Microbial dysregulation in infancy may trigger or accelerate JIA development. Environmental risk factors have a stronger impact on genetically predisposed children. This study is the first to implicate microbial dysregulation in JIA at such an early age, with many bacterial taxa associated with risk factors. These findings provide opportunities for intervention or early screening and offer new insights into JIA pathogenesis.

Funding
Barndiabetesfonden; Swedish Council for Working Life and Social Research; Swedish Research Council; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden; JDRF-Wallenberg Foundation; Linköping.

医療・健康
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