The Research Progress on Intestinal Stem Cells and Its Relationship with Intestinal Microbiota

Abstract

The intestine is home to trillions of microorganisms, and the vast diversity within this gut microbiota exists in a balanced state to protect the intestinal mucosal barrier. Research into the association of the intestinal microbiota with health and disease (including diet, nutrition, obesity, inflammatory bowel disease, and cancer) continues to expand, with the field advancing at a rapid rate. Intestinal stem cells (ISCs) are the fundamental component of the mucosal barrier; they undergo continuous proliferation to replace the epithelium, which is also intimately involved in intestinal diseases. The intestinal microbiota, such as Lactobacillus, communicates with ISCs both directly and indirectly to regulate the proliferation and differentiation of ISCs. Moreover, Salmonella infection significantly decreased the expression of intestinal stem cell markers Lgr5 and Bmi1. However, the detailed interaction of intestinal microbiota and ISCs are still unclear. This review considers the progress of research on the model and niches of ISCs, as well as the complex interplay between the gut microbiota and ISCs, which will be crucial for explaining the mechanisms of intestinal diseases related to imbalances in the intestinal microbiota and ISCs.

Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?

“…Finally, if pharmacological targeting of LGR5 proves to be non-viable, ineffective, too toxic, or expensive then perhaps other avenues for LGR5 targeting in CRC treatment could be pursued. There are a number of studies showing that dietary factors such as high fat, 88 curcumin, 89 vitamin D, 90 and alcohol, 91 along with alterations to the gut microbiota, 92 can affect both the frequency and tumourigenicity of LGR5 + cells, and LGR5 expression level. Such approaches to modulate LGR5 expression in tumour cells would be cost-effective if they could be proven to reduce CRC incidence or promote tumour regression.…”

Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan interaction in aging

“…Reduced ISC Wnt/β‐catenin activity and decreased Wnt5a and Wnt11 expression were observed in mice lacking commensal bacteria . Several studies have also shown a clear link between Toll‐like receptor signaling by the microbiome and ISC Wnt signaling . Thus, an abnormal microbiome may disrupt ISC Wnt signaling required to maintain normal intestinal crypt cell fate and barrier function and may be a critical cause of inflammaging resulting in aging‐associated bone loss, as seen in the ovarectomized mouse model …”

“…135 Several studies have also shown a clear link between Toll-like receptor signaling by the microbiome and ISC Wnt signaling. 136 Thus, an abnormal microbiome may disrupt ISC Wnt signaling required to maintain normal intestinal crypt cell fate and barrier function and may be a critical cause of inflammaging resulting in aging-associated bone loss, as seen in the ovarectomized mouse model. 121,137 As we have mentioned above, although genetic evidence has shown that LRP5 has crucial roles in regulating bone mass, the mechanisms by which LRP5 controls bone formation remain unclear.…”

Glutamine supplementation improves intestinal cell proliferation and stem cell differentiation in weanling mice

“…Various parameters (e.g. intestinal microbiota, intestinal metabolites, and cellular signaling pathways) regulate the proliferation and differentiation of intestinal stem cells, leading to the alteration in the number of each type of cells and the progression of various diseases like inflammatory bowel disease, infection, and cancer ( 7 , 9 – 15 ). Glutamine is a primary metabolic fuel of small intestinal enterocytes and is essential for the viability and growth of intestinal cells by serving as a precursor for synthesis of nucleotides, glucose, amino acids, and proteins ( 16 , 17 ).…”