Changes in gut microbiota underlie autoimmune responses during pregnancy and lactation in lupus mouse model

Maternal physiology and metabolism during pregnancy adjust so the fetus may grow healthy. As part of these changes, the gut microbiota evolves towards a pro-inflammatory profile, which contributes to a healthy pregnancy. Even so, the extent to which gut microbiota alterations induced by pregnancy and lactation may change autoimmune mechanisms that are involved in disease has not yet been explored.

A new mice study, led by Dr. Xin M. Luo from the Virginia-Maryland College of Veterinary Medicine (USA), has found that changes in gut microbiota composition can shape autoimmune responses in lupus during pregnancy and lactation.

Imbalances in the gut microbiota have been observed in different autoimmune diseases such as systemic lupus erythematosus. Although lupus patients usually experience severe disease flare-ups post-delivery, the connection between the gut microbiota alterations induced by pregnancy and lactation and the postpartum exacerbation of lupus had not been explored previously.

In a lupus mouse model, the authors showed that both pregnancy and lactation led to significant changes in the composition and diversity of gut microbiota when compared with age-matched mice without pregnancy or lactation.

The oral administration of vancomycin, an antibiotic which is not absorbed within the gastrointestinal tract, exacerbated lupus postpartum, whereas it led to an attenuation of lupus in mice that were not pregnant or lactating. The mechanisms by which vancomycin acted in mice in the postpartum period included a decreased anti-inflammatory response mediated by regulatory T and B cells and increased production of pro-inflammatory interferon-gamma. Such dysregulation in the pro- and anti-inflammatory balance was not observed in mice with lupus that were not pregnant or lactating.

These initial findings clearly suggest that changes in the gut microbiota induced by antibiotic treatment may mediate the exacerbation of lupus during pregnancy and lactation.

Vancomycin-treated mice showed an increase in Lactobacillus animalis in the gut, whereas there was a depletion in the total gut bacterial load.

As observed after treatment with vancomycin, the oral administration of L. animalis led to an exacerbation of lupus postpartum—consisting of worsened splenomegaly and proteinuria—while this did not affect the course of the disease in mice that were not pregnant or lactating.

Specifically, L. animalis acted by inhibiting the serum enzyme indoleamine 2,3-dioxygenase alongside a differential production of immunosuppressive and pro-inflammatory mediators in the postpartum period. These data showed that the enriched L. animalis was involved in the vancomycin-driven effects on decreased T regulatory cells and increased pro-inflammatory cytokines.

On the whole, shared mechanisms between vancomycin and L. animalis caused a worsening of lupus disease in mice with regards to pro-inflammatory responses within the postpartum period. However, neither case involved changes in intestinal barrier function, which is something that acts as a trigger of the disease in patients with lupus.

These findings show – in mice – gut microbiota’s contribution to the connection between pregnancy and the exacerbation of lupus. To what extent gut microbiota’s role in exacerbating lupus is plausible in pregnant women deserves further research, especially through follow-up studies and by correlating gut microbiota findings in health-related outcomes.

Reference:

Mu Q, Cabana-Puig X, Mao J, et al. Pregnancy and lactation interfere with the response of autoimmunity to modulation of gut microbiota. Microbiome. 2019; 7:105. doi: 10.1186/s40168-019-0720-8.

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GMFH Editing Team
GMFH Editing Team