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Gut Microbiome Affects Response to Immunotherapy

Fuerst, Mark L.

doi: 10.1097/01.COT.0000557867.95650.35
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microbiome; immunotherapy; AACR

microbiome; immunotherapy; AACR

ATLANTA—Dietary factors that affect the gut microbiome may influence response to immunotherapy in melanoma patients.

The first clinical study to report on the relationship between diet, microbiome, and response to anti-programmed cell death-1 (PD-1) checkpoint inhibitors found melanoma patients who consumed a high-fiber diet had greater gut microbiome diversity and a better response to treatment.

“We found that diet and supplements appear to have an effect on a patient's ability to respond to cancer immunotherapy, most likely due to changes in their gut microbiome,” said Christine Spencer, PhD, a research scientist at the Parker Institute for Cancer Immunotherapy. “The gut microbiome plays a big role in moderating the immune system, so the idea that we could potentially change the microbiome—whether by diet or other means—to improve response to immunotherapy treatment is really exciting.”

Spencer presented the results of the study (Abstract 2838/24) at a media preview of the American Association for Cancer Research (AACR) Annual Meeting 2019.

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Study Details

Previously, the researchers had reported that melanoma patients with a diverse gut microbiome enriched in bacteria of the Ruminococcaceae family were more likely to respond to anti-PD-1 treatment (Science 2018:359(6371):97-103).

“In our current study, we wanted to look at how diet and supplements affect the microbiome and modulate responses to checkpoint immunotherapy,” noted Spencer.

Utilizing prospectively collected fecal samples from 113 melanoma patients who started treatment at the University of Texas MD Anderson Cancer Center in Houston, the researchers characterized the diversity and type of bacterial species found in the gut microbiome. They found that higher microbiome diversity was associated with response to therapy regardless of treatment type, and that the gut microbiome did not significantly differ based on age, sex, and body mass index.

Among patients who completed baseline dietary surveys, researchers found that eating whole grains, fruits and vegetables, and a high-fiber diet was positively associated with bacteria previously shown to confer response to anti-PD-1 treatment. Diets high in added sugars and processed meat were negatively associated with these bacteria.

In a subset of 46 patients treated with anti-PD-1 immunotherapy, the researchers found that patients who consumed a high-fiber diet were about five times as likely to respond to anti-PD-1 treatment compared to patients who consumed a low-fiber diet.

“We know from prior research that eating a higher-fiber diet has a lot of health benefits. But with this preliminary research on cancer patients and the microbiome, it appears that fiber is also linked to a better response to immunotherapy,” Spencer stated.

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Use of Probiotics

Among all surveyed patients, more than 40 percent reported use of probiotic supplements, which was associated with lower gut microbiome diversity. Spencer noted that low gut microbiome diversity has been linked to poorer response to checkpoint inhibitor immunotherapy.

“There's a perception that taking probiotics improves gut health, but our results, although early, suggest that may not be the case for cancer patients,” she said.

Probiotics are live bacteria and yeasts found primarily in the digestive system, and they are commonly found in fermented foods, such as kefir, yogurt, kimchi, and sauerkraut. However, probiotic supplements are not regulated by the FDA.

“Based on these preliminary results, we need to reconsider use of over-the-counter probiotics in patients with cancer, at least until we have more data supporting their potential safety and efficacy,” said senior author Jennifer Wargo, MD, MMSc, a Parker Institute investigator at MD Anderson, where she is Associate Professor of Surgical Oncology and Genomic Medicine.

The researchers noted the limitations of the study include a small sample size and a reliance on self-reported diet and supplement use.

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Research Outcomes

Spencer said the main takeaways of the study are “food [and] supplements may impact response to cancer immunotherapy, likely via the gut microbiome. More fiber is good. High-fiber diets have been linked to health benefits. This study shows fiber linked to a better response to cancer immunotherapy.” She suggested that physicians talk to their patients about any over-the-counter supplements they are taking, including probiotics.

In conclusion, Spencer stated: “Diversity of the gut microbiome varies by response regardless of treatment type. While preliminary, this data points to the idea that the gut microbiome in melanoma patients may be negatively influenced by probiotics and could be targeted by dietary manipulation.”

Larger, prospective and interventional studies are needed to assess the relationships between host lifestyle factors, the gut microbiome, and response to melanoma therapies, she added. The researchers plan to validate the data in large cohorts, including the association of antibiotic intake and response.

AACR President Elizabeth M. Jaffee, MD, who is Deputy Director, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, commented: “How gut bacteria enhances cancer development is an exciting area of research that is making headway. Important publications in the past several years have discussed how bacteria influence cancer progress, empowered through the diet to influence response to immunotherapy.” She noted that this research is in the early stage and it has yet to be determined which bacteria are good or bad.

“Those who eat a high-fiber diet respond better to immunotherapy. This new data provides a possible mechanism to explain why high-fiber diets benefit cancer patients,” said Jaffee. “However, it can be detrimental when cancer patients take probiotics.” She warned clinicians to caution patients about taking probiotic supplements along with immunotherapy.

Mark L. Fuerst is a contributing writer.

Wolters Kluwer Health, Inc. All rights reserved.
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