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. 2023 Jan 1;15(1):221.
doi: 10.3390/nu15010221.

Celiac Disease Predisposition and Genital Tract Microbiota in Women Affected by Recurrent Pregnancy Loss

Luca Masucci  1   2 , Silvia D'Ippolito  3 , Flavio De Maio  2 , Gianluca Quaranta  2 , Roberta Mazzarella  3 , Delia Mercedes Bianco  1 , Roberta Castellani  3 , Annalisa Inversetti  4   5 , Maurizio Sanguinetti  1   2 , Antonio Gasbarrini  6   7 , Giovanni Scambia  3   8 , Nicoletta Di Simone  4   5
Affiliations

Celiac Disease Predisposition and Genital Tract Microbiota in Women Affected by Recurrent Pregnancy Loss

Luca Masucci et al. Nutrients. .

Abstract

The incidence of Idiopathic Recurrent Pregnancy Loss (RPL) is doubled in patients suffering from Celiac Disease (CD) compared to healthy populations. CD genetic components are HLA class II genes known as HLA-DQ2 and DQ8. Genetically susceptible women can remain asymptomatic even though they are exposed to a doubled risk of RPL compared to the general population. Furthermore, CD has been associated with microbiota alterations. The aim of this study is to evaluate endometrial and vaginal microbiota in HLA-DQ2/DQ8 positive and negative RPL patients compared to healthy pregnant women. Endometrial and vaginal microbiota of 3 subgroups were evaluated: 15 HLA-DQ2/DQ8 positive RPL women, 25 HLA DQ2/DQ8 negative RPL women (for a total of 40 RPL women) and 7 healthy fertile controls with previous uncomplicated pregnancies (all HLA-DQ2/DQ8 negative). The 2 RPL subgroups (HLA-DQ2/DQ8 positive and negative) showed a different endometrial and vaginal composition in the Lactobacillacae family compared to controls: Lactobacillus acidophilus was absent both in the vaginal and endometrial samples of RPL women, while Lactobaciluus iners, which can favor a less stable vaginal microbiota, was found only in RPL women (26.4% in HLA DQ2/DQ8 positive and 22.1% HLA DQ2/DQ8 negative) in both the vaginal and endometrial districts. In conclusion, both HLA DQ2/DQ8 positive-RPL and HLA DQ2/DQ8 negative-RPL women showed different endometrial and vaginal microbiota composition compared to healthy controls.

Keywords: celiac disease predisposition; genital microbiota; recurrent pregnancy loss.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PERMANOVA statistical test showed a significant change between control and HLA-DQ2/DQ8 positive-RPL women in (p = 0.037, R2 = 0.109) in endometrial samples (Shannon diversity). No significant differences were observed between RPL women independent of the HLA-DQ2/DQ8 state (p = 0.900) (A,B). Differences in the microbial population between healthy control and women with CD predisposition were assessed using weighted Unifrac beta diversity. The obtained distance matrix was represented as PCoA, showing a clusterization among the three studied groups (C). Legend: CTR = control; Low = HLA-DQ2/DQ8 negative-RPL women; High = HLA-DQ2/DQ8 positive-RPL women. ** significantly different.
Figure 2
Figure 2
(A) Phylum level: Relative abundance detected in endometrial samples. CTR = control; Low = HLA- DQ2/DQ8 negative-RPL; High= HLA-DQ2/DQ8 positive-RPL. (B) Genus level: Relative abundances detected in endometrial samples. Legenda: CTR = control; Low = HLA-DQ2/DQ8 negative-RPL; High: HLA-DQ2/DQ8 positive-RPL.
Figure 3
Figure 3
PERMANOVA statistical test confirmed a no significant change among the three groups (p = 0.224, R2 = 0.056) in vaginal samples. Legend: CTR = control; Low = Low-risk for CD; High: High-risk for CD.
Figure 4
Figure 4
(A) Phylum level: Relative abundance detected in vaginal samples CTR = control; Low = HLA DQ2 DQ8 negative-RPL; High: HLA DQ2 DQ8 positive-RPL. (B) Genus level: Relative abundances detected in vaginal samples. Legenda: CTR = control; Low = HLA DQ2 DQ8 negative-RPL; High: HLA DQ2 DQ8 positive-RPL.
Figure 5
Figure 5
Lactobacillus spp.: relative abundances in all group specimens. Legend: CTR = control; Low = HLA DQ2 DQ8 negative-RPL; High: HLA DQ2 DQ8 positive-RPL.
See this image and copyright information in PMC

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