**3. Mother to child transfer of IBD**

Pre- as well as post-natal bacterial colonisation plays a significant role in sculpting the immune system. Microbes transmitted from mother to infant presumably adapt to and persist in the infant gut than non-maternally acquired strains. Human trials have demonstrated the influence of maternal health status and microbiology on the development of the neonatal microbiome and immune system [27, 28]. The role of IBD in the maternal microbiome composition during pregnancy and its impact on the offspring's microbiome was investigated by Torres *et al.* by sampling pregnant women with and without IBD for their stool and saliva at each trimester, combined with their clinical and obstetric records. Post-delivery, the neonates were pursued with serial stool samples at time points of 7, 14, 30, 60, and 90 days, respectively, along with thorough health and exposure metadata. Stool samples from mother– baby pairs were then gavaged into 6–8 weeks old germ-free mice (GFM) for their immune phenotyping. 16S rRNA sequencing and microbiome analysis of the samples revealed that women with IBD maintained altered gut bacterial diversity throughout the pregnancy, with an enrichment of *Gammaproteobacteria* and a reduction in *Bacteroidetes*, compared with healthy controls. Offsprings to the IBD mothers demonstrated similarity to the bacterial diversity and composition trends of the mothers, to at least 3 months after birth compared with the offsprings to control mothers [29]. GFM inoculated with the stools from the third trimester IBD mother and 90-days infant showed a considerable reduction in the microbial diversity and fewer classswitched memory B cells and regulatory T cells in the colon, indicating the possible role of microbial factors from maternal IBD in influencing the immune system of the offspring [30].

Another study by Kim *et al.* made use of fecal calprotectin (FC) to monitor intestinal inflammation in pregnant women and their offsprings. FC is a non-glycosylated, calcium- and zinc-binding protein with antimicrobial, antiproliferative, and immunomodulatory properties, and it is used as a surrogate marker of intestinal inflammation [31]. FC levels decreased gradually in mothers with IBD during the 3 trimesters of pregnancy, contrary to the control mothers in which small gradual increase in FC levels was reported [32]. The rising levels of FC in healthy pregnancy correlated with the increase in pro-inflammatory phylum Proteobacteria and a decrease in anti-inflammatory *Faecalibacterium* [33]. Babies born to mothers with IBD presented significantly higher FC levels compared with control babies starting at 2 months of life and throughout 36 months. FC levels in both pregnant women with IBD and

their babies were positively correlated with *Streptococcus* abundance and negatively correlated with that of *Alistipes* [32]. Consequently, maternal IBD has the potential to adversely affect the offspring's intestinal milieu during early life after birth, which can have significant health-related consequences later.
