# An Insight into Probiotics Bio-Route: Translocation from the Mother's Gut to the Mammary Gland
## 4 Microbial Transmission: Solving the Labyrinth Path
### Cross-Contamination from Infants' Oral Cavity
#### 4.3.2 Mucosal Sampling and Migration of Dendritic Cells
Several studies have suggested that DCs such as CD11c+ and CX3 CR1+ macrophage cells can extend their trans-epithelial dendrites through the tight junction in the intestinal epithelium to capture luminal antigens or bacteria [33; 99; 100]. [PERSON] et al. used 2-photon microscopy in live mice to evaluate the microbial sampling by CD103+ DCs in the mesentery lymph nodes [101]. These DCs engulfed _Salmonella_ bacteria in the lamina propria and rapidly retracted toward the soma [101]. The study reported that CD103+ DCs translocated _Salmonella_ bacteria in two steps [102; 103; 104]. First, some DCs were found to sense the presence of bacteria and started to secrete chemokines to stimulate more DCs to migrate to the epithelium. Then, the newly arrived DCs extended  
Figure 3: GALT containing lamina propria, Peyer’s patches, and mesenteric lymph nodes (MALT). DCs are present in the lymphoid compartments. their dendrites toward the lumen by penetrating the tight junction between intestinal cells. The dendrites were extended in response toward the chemokines and started to engulf the bacteria. The DCs will become mature plasma cells when returning to the lamina propria through lymphatic vessels (Figure 3). The presence of antigens on DCs stimulated T cells to initiate adaptive immunity [101; 104]. The maternal microbiota are believed to be transferred to the mammary glands by DCs through the above explained lymphatic system and the entero-mammary pathway [105; 106]. However, the precise selection of microbiota and how DCs differentiate commensal or pathogenic bacteria are yet to be explored. Human gastrointestinal microbiota include a large and diverse community including hundreds of commensal bacteria as well as pathogenic species. The pathogenic microflora induces specific inflammatory responses against commensal microbiota in the competitive environment. [PERSON] et al. demonstrated that germ-free mice injected with Gram-negative obligate anaerobes originating from the intestinal microbiota consortium would be sufficient to induce spontaneous colitis [107]. The activation of inflammatory responses by the intestinal microflora could mediate subsequent host pattern-recognition receptors [108]. This also leads to the recruitment of specific macrophages and DCs to activate adaptive immune responses [107]. These mononuclear phagocytic cells (macrophages and DCs), which normally reside in the intestinal lamina propria, also play a critical role in preventing inappropriate activation of inflammatory responses to the normal microflora [107; 108]. But how does the immune system discriminate between commensal and pathogenic bacteria? Several commensal bacteria including _Bifidobacteria_ strains have been found to induce tolerance in monocyte-derived DCs, which can recognize the specific pathogen-associated molecular patterns [99; 108]. This step could help to precisely discriminate the intestinal microflora. This finding has been utilized to explain DCs translocation of non-pathogenic gastrointestinal bacterial strains like _Lactobacillus_ and _Bifidobacterium_ spp. [10]. We suggest that these translocation patterns could explain the entero-mammary pathway transfer of gut microbiota into mammary glands (Figure 4). DCs sample the commensal bacteria from maternal gut during pregnancy or after birth. After luminal sampling, DCs could travel in the lymphatic systems and reach axial lymphatic nodes. Then, DCs or microbes could migrate to the internal mammary lymphatic node [39; 100; 109]. Bioluminescence imaging was performed by [PERSON] et al. to show that lactic acid bacteria could be transported in vivo during pregnancy in mice [6]. In this study, two strains of _L. lactis_ MG1614 and _L. salivarius_ PS2 were genetically modified to harbor luminescent response producing lux operon genes. Both strains could be isolated, and the lux genes were detected by PCR techniques from either milk or mammary gland biopsies after their oral administration to pregnant mice [6].