Oral probiotics increased the proportion of Treg, Tfr, and Breg cells to inhibit the inflammatory response and impede gestational diabetes mellitus

Abstract

Background Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM. Methods GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels. Results GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-β and IL-10, preventing inflammation and preserving mouse pregnancy. Conclusion Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.

Relationship between gut microbiota and the pathogenesis of gestational diabetes mellitus: a systematic review

“…Disturbed gut microbiota produces large amounts of LPS, which leads to a variety of different biological activities. For example, Liang et al (2023) found that oral administration of probiotics significantly reduced Gram-negative bacterial counts, lowered inflammatory factor levels, and prevented GDM. Prebiotics such as isomaltodextrin have beneficial effects on chronic inflammation-associated insulin resistance by restoring the intestinal barrier and reducing circulating endotoxin levels (Hann et al, 2019).…”

Maternal gut microbiota in the health of mothers and offspring: from the perspective of immunology

“…After the intervention, hypersensitive C-reactive protein (hs-CRP), TNF-α, and IL-6 levels were significantly reduced in women with GDM who were treated with probiotics compared to the placebo group ( 235 ). A recent study proved that oral probiotics increased Tregs, Tfrs and Bregs and decreased proinflammatory cytokines to prevent inflammation in mice with GDM ( 47 ), which showed the effect of probiotics on regulating the immune response. Additionally, probiotics can reverse the phenotype of GDM through the metabolism pathways of amino acids, bile acids, porphyrin, and chlorophyll ( 236 ).…”

“…When fed with a diet enriched in prebiotics, the abundance of Tregs increased in the placenta, and Bregs increased in both the placenta and the uterus, followed by the alteration of gut microbiota ( 46 ). It has been proved recently that oral probiotics also increased Tregs, Bregs and follicular regulatory T cells (Tfr), as well as IL-10 and transforming growth factor-β (TGF-β), while decreased TNF-α and IL-6 to prevent inflammation in mice with GDM ( Figure 1 ) ( 47 ). In a sow model, a higher abundance of Bacteroides fragilis was associated with higher levels of LPS, IL-1β and IL-6 as well as increased intestinal permeability ( 48 ).…”

“…Recent studies found that the insufficiency of circulating dopamine, imbalanced production of SCFAs, and excessive inflammation resulting from the dysbiosis of the gut microbiota led to the development of GDM ( 133 , 135 , 136 ). Meanwhile, restoring the balance of maternal gut microbiota limited the inflammatory response by increasing the production of Tregs, Tfrs, Bregs in the GDM mice model ( 47 ). Another study proposed that gut bacteria were responsible for shifting indoleamine 2,3-dioxygenase-dependent tryptophan anaerobic metabolism to kynurenine production, leading to intestinal inflammation and gestational insulin resistance in the mice model ( 171 ).…”

Nutrition during pregnancy: Influence on the gut microbiome and fetal development

“…Pregnancy is a unique biological process in which orchestrated hormonal, metabolic and immunological changes promote fetal nourishment and development within the maternal womb. These physiological adaptations interact dynamically with the microbiota resident in the gut, so that maternal hormonal and metabolic changes shape the structure and diversity of the bacterial community, 49,50 and conversely, microbial byproducts modulate pregnancy‐associated processes including placental development 51,52 and feto‐maternal tolerance 53–56 . Indeed, the bidirectional nature of these interactions is evidenced by the increasing amount of research demonstrating the direct link between imbalances of the microbiota and adverse pregnancy outcomes such as preeclampsia, fetal growth restriction, preterm birth, and gestational diabetes (reviewed in 57 ).…”