Modulation of Gut Microbiota by Oral Sialic Acid: A Mechanistic Study

Background：Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies worldwide, ranking third in incidence and second in mortality among all cancers. Surgical resection remains the primary treatment for CRC, particularly for early- and mid-stage patients, as it effectively removes tumor tissue and prolongs survival. However, postoperative anastomotic healing failure (e.g., anastomotic leakage) is a severe complication of colorectal surgery, with an incidence rate of 5%-20%. Anastomotic leakage not only significantly increases postoperative mortality but also prolongs hospital stays, escalates medical costs, and imposes a heavy burden on both patients and healthcare systems. The pathogenesis of anastomotic leakage is complex, involving factors such as local ischemia, surgical technique, infection, and gut microbiota dysbiosis. In recent years, with advancements in microbiomics research, the role of gut microbiota in anastomotic healing has gained increasing attention.

During malignant transformation, colorectal cancer cells exhibit significantly upregulated expression of sialic acid (SA) on their cell surfaces. Sialic acid, a class of nine-carbon monosaccharides widely distributed on mammalian cell surfaces, participates in cell-cell recognition, immune regulation, and host-microbe interactions. Studies have shown that shed sialic acid from colorectal tumor cells enters the intestinal lumen, serving as a critical nutrient source for gut microbes. Notably, certain pathogens (e.g., Escherichia coli, Klebsiella pneumoniae) can utilize sialic acid as a carbon source to promote their proliferation and colonization. These pathogens may impair anastomotic healing through multiple mechanisms: first, by disrupting the intestinal mucosal barrier and exacerbating local inflammation; second, by inhibiting epithelial cell repair and delaying tissue regeneration; and third, by producing toxins or metabolites that further damage local tissues. Thus, colorectal tumor-derived sialic acid may indirectly increase the risk of postoperative anastomotic healing failure by nourishing specific pathogens.

Although existing research suggests that sialic acid from colorectal tumors influences the gut microenvironment by feeding pathogens, the specific mechanisms underlying its impact on postoperative anastomotic healing remain unclear. This hypothesis requires experimental validation. Our preliminary animal studies have demonstrated that oral administration of sialic acid impairs rectal anastomotic healing in mice by modulating gut microbiota. This finding indicates that sialic acid may affect postoperative anastomotic tissue repair and inflammatory responses by altering gut microbiota structure. However, research on the effects of sialic acid on the human gut microbiota remains limited. Based on this background, the present study aims to characterize the impact of sialic acid on gut microbiota by analyzing fecal samples collected from volunteers following oral sialic acid intervention.

Study Design： This study employs a before-after self-control trial design, recruiting 42 volunteers to take oral sialic acid and collecting fecal samples before and after the intervention. Specifically, the control group specimens were fecal samples collected before oral sialic acid administration, while the experimental group specimens were fecal samples collected after oral sialic acid administration.

Primary Objective:Alterations in Gut Microbiota Structure