Bacteriophages and their potential for treatment of gastrointestinal diseases

Abstract

Although bacteriophages have been overshadowed as therapeutic agents by antibiotics for decades, the emergence of multidrug-resistant bacteria and a better understanding of the role of the gut microbiota in human health and disease have brought them back into focus. In this Perspective, we briefly introduce basic phage biology and summarize recent discoveries about phages in relation to their role in the gut microbiota and gastrointestinal diseases, such as inflammatory bowel disease and chronic liver disease. In addition, we review preclinical studies and clinical trials of phage therapy for enteric disease and explore current challenges and potential future directions.

Figure 1.. Intestinal phageome of healthy individuals and patients with inflammatory bowel disease.

Left: healthy individual; Right: patients with inflammatory bowel disease. Compared with healthy individuals, patients with inflammatory bowel disease have a higher relative abundance of Caudovirales compared with Microviridae, and different compositions of Caudovirales families.

Figure 2.. Manipulation of the gut microbiota by phages.

(a) Phage therapy in Crohn’s disease. Adherent-invasive E. coli stimulates antigen-presenting cell (APC) driving Th17 responses, phages targeting adherent-invasive E. coli were found to be beneficial of DSS-induced colitis. (b) Phage therapy in alcoholic liver disease. Cytolysin positive E. faecalis translocates from the gut to the liver, directly damaging hepatocytes. Phages against cytolysin positive E. faecalis could protect mice from alcoholic liver disease. (c) Phage therapy in colorectal cancer. Streptococcus gallolyticus subsp. gallolyticus (Sgg) upregulates β-catenin, stimulating cancer cell proliferation. Phage therapy might be a promising treatment option.

Figure 2.. Manipulation of the gut microbiota by phages.

(a) Phage therapy in Crohn’s disease. Adherent-invasive E. coli stimulates antigen-presenting cell (APC) driving Th17 responses, phages targeting adherent-invasive E. coli were found to be beneficial of DSS-induced colitis. (b) Phage therapy in alcoholic liver disease. Cytolysin positive E. faecalis translocates from the gut to the liver, directly damaging hepatocytes. Phages against cytolysin positive E. faecalis could protect mice from alcoholic liver disease. (c) Phage therapy in colorectal cancer. Streptococcus gallolyticus subsp. gallolyticus (Sgg) upregulates β-catenin, stimulating cancer cell proliferation. Phage therapy might be a promising treatment option.

Figure 3.. Potential applications of phages.

Apart from targeting their bacterial hosts, phages might also interact with the human body and could thereby have multiple effects on human health and diseases.