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The Microbiome, Diet and Cancer Immunotherapy

The Microbiome, Diet and Cancer Immunotherapy

Authored by: George M. Pikler, M.D., Ph.D., FACP

Our gastrointestinal tract represents a large microbial ecosystem, housing several trillion of bacteria and other microbes. Estimated to harbor a hundred times more unique genes than the human genome, the effect of the microbiome extends beyond its local intestinal niche to systemic host tissues and immune cells. Its composition is influenced by host genetics, diet, environment, and factors including antibiotic use which can alter gut balance.

In the last decade, growing knowledge of the human microbiome, fueled by recent advances in genome sequencing, has recognized the human microbiome as a key area of interest in the pathophysiology of various human diseases including cancer tumorigenesis, progression and in disease outcome.1 Vast amount of data has implicated pathogenic microbes harboring specific virulence factors in driving the carcinogenic activity of various malignancies including colorectal, gastric, and pancreatic cancer.

Treatment of various cancers using immune checkpoint inhibitors (ICIs) therapy has considerably advanced with the targeting of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4). However, although promising, these novel ICI strategies have considerable interindividual variation, and the effect on treatment of tumors has been inconsistent among tumor types.2

Scientists have found that patients who harbor certain gut bacteria have better responses to immunotherapy than patients who lack them.3 Scientists at the University of Chicago discovered that mice with a strain of gut bacteria known as Bifidobacterium had a stronger immune response against melanoma tumors than mice who lacked the bacteria. They found that giving Bifidobacterium to the deficient mice slowed tumor growth. What’s more, combining the bacteria with a checkpoint inhibitor nearly abolished the tumors.

A research team at MD Anderson found that melanoma patients reporting high fiber (prebiotic) meals had a better response to checkpoint immunotherapy compared with those patients reporting a low-fiber diet. The most marked benefit was observed for those patients reporting a combination of high fiber consumption and no use of over-the-counter probiotic supplements.

The team examined the diets of 128 melanoma patients and found that those who regularly ate large amounts of fiber from fruits, vegetables, and other plant foods had better outcomes on immunotherapy than patients who ate the least amount of fiber. Their data provided early insights as to how diet-related factors may influence the immune response.

They conducted a clinical trial testing whether changing the patients’ diet could change their microbiome. They based their trial on the knowledge that some of the gut microbes that appear to improve how patients respond to immunotherapy are known to thrive on fiber. These are bacteria that help break down and utilize starch and fibers. In the trial, patients were given daily meals that included as much as 50 grams of daily fiber from foods like beans, lentils, farro, brown rice, fruits, and vegetables — about twice the recommended amount of 25 to 30 grams of fiber a day. By comparison, the average American diet contains roughly 15 grams a day.

Their findings4 showed that every five-gram increase in daily fiber intake was associated with a 30 percent lower risk of death or cancer progression.

1Doocey, C.M. et al. The impact of the human microbiome in tumorigenesis, cancer progression, and biotherapeutic development. BMC Microbiol. 2022 Feb 12;22 (1):53

2 Longsha, L and Shah, K. The Potential of the Gut Microbiome to Reshape the Cancer Therapy Paradigm. A Review. JAMA Oncol. 2022;8(7):1059-1067.

3 Roviello, G, et al._The gut microbiome and efficacy of cancer immunotherapy. Pharmacology & Therapeutics. 2022 Mar; 231, 107973

4 Spencer, C.N, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 2021, Dec 23; 374(6575), 1632-1640.

Authored by:
George M.Pikler, M.D., Ph.D., FACP
Lead Oncology Advocate N1X10

Dr. Pikler graduated summa cum laude from the Central University of Ecuador School of Medicine in 1968. His postdoctoral training included an internship in internal medicine at Greater Baltimore Medical Center in Baltimore, MD, a residency in internal medicine and a doctoral degree in molecular medicine at the Mayo Clinic in Rochester, MN. The American Cancer Society awarded him a fellowship in medical oncology and hematology at M.D. Anderson & Tumor Institute in Houston, TX.

With training certifications in internal medicine and oncology, Dr. Pikler and his family moved to Tulsa, OK where he established and was the President of Cancer Specialists, Inc, a boutique oncology-hematology clinical research private practice. In addition, he was the chief of the oncology at Hillcrest Medical Center, a teaching hospital for 20 years and associate professor of medicine, oncology-hematology at the University of Oklahoma, Tulsa Medical College. He was one of the founders of the Southern Association of Oncology Practices and subsequently the National Medical Director for the International Oncology Network, AmerisourceBergen’s Oncology Division.

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