Review: Baseline Gut Microbiota May Predict Immunotherapy Responses

Review findings outline the gut microbiome's potential impact on immunotherapy responses.

Dietary interventions with locally available fruits, vegetables, and whole grains might be an affordable and safe approach to enhancing the diversity of gut microbiota before immunotherapy, which may potentially improve patients’ treatment responses, according to recently published review findings.

Although alterations in the gut microbiota have previously been associated with several functional gastrointestinal disorders, this community of microorganisms has also been linked with genitourinary malignancies, including bladder, kidney, and prostate cancers, authors explained.

In addition, “recent intriguing evidence from several human clinical trials has suggested that the composition and diversity of the gut microbiota at baseline influences response to cancer immunotherapy.”

To better understand whether diets could enhance patients’ responses to cancer therapies by manipulating the gut microbiota, researchers carried out a systematic review searching articles published on PubMed, Web of Science, Sciencedirect and Scopus. They included the following terms: fruits, vegetables, whole grains, gut microbiota, human clinical trials, and cancer therapy.

One trial included in the review assessed outcomes of those on the Mediterranean diet and individuals habitually following omnivore, vegetarian, or vegan diets. Results showed that participants (n = 153) “increased levels of fecal short chain fatty acid (SCFAs), Prevotella, and some fiber-degrading Firmicutes.”

An additional study investigating the consumption of whole grains for 6 weeks by healthy participants revealed those who consumed whole grains, but not refined grains, exhibited increased levels of plasma alkylresorcinols and stool weight and frequency, in addition to higher levels of stool acetate and SCFAs.

“These changes associated with increased levels of Lachnospira, which produces SCFAs, and decreased levels of Enterobacteriaceae, which are pro-inflammatory,” authors wrote.

One other study found that even short-term consumption of whole grains and/or brown rice yielded changes in the gut microbiota that aligned with improvements in individuals’ physiological measures.

Despite these positive findings seen in healthy individuals, studies have yielded conflicting results among overweight or obese participants.

A larger study that followed 123 overweight/obese individuals for 9 weeks who consumed a whole grain-based diet revealed participants exhibited “significantly reduced fecal levels of Enterobacteriaceae and Desulfovibrionaceae, which are endotoxin-producing pathogens. In contrast, levels of Bifidobacteriaceae, which protect the gut barrier, increased,” authors wrote.

“Levels of lipopolysaccharide-binding protein, TNF-α, and IL-6 decreased, and levels of adiponectin increased, suggesting that whole grain intake may ameliorate inflammatory and metabolic phenotypes,” they added.

Although several other trials showed consuming fruits, vegetables and whole grains did not alter participants’ gut microbiota, researchers noted that components of these food stuffs can suppress inflammation and improve gut health by modulating the immune system before changes in the gut microbiota become obvious.

Previous human studies also suggested gut microbiota composition at baseline may affect cancer immunotherapy responses.

“One trial of ipilimumab studied 26 metastatic melanoma patients, comparing those whose guts were enriched with the Faecalibacterium genus and other Firmicutes at baseline with those who were enriched in Bacteroides. The former had longer progression-free survival and overall survival as well as more frequent colitis induced by ipilimumab,” researchers said.

In a trial of 112 individuals with melanoma treated with anti-programmed cell death 1 protein (PD1) immunotherapy, those who responded to treatment had increased alpha diversity and abundant Ruminococcaceae family members in their gut microbiotas, while their anabolic pathways were upregulated, and their systemic and antitumor immunity was enhanced, according to authors.

Several additional clinical trials are ongoing in which researchers are manipulating the gut microbiota via lifestyle changes or probiotics, synbiotics or fecal transplantation in an effort to improve responses to cancer therapy.

Most trials already completed focused patients with melanoma and revealed how baseline gut microbiota composition impacted responses to immunotherapy. According to researchers, “these approaches warrant testing in non-small-cell lung cancer and renal cell carcinoma patients.”

Reference

Wang L, Mo YY, Huang Y, et al. Effects of dietary interventions on gut microbiota in humans and the possible impacts of foods on patients’ responses to cancer immunotherapy. eFood. Published online July 23, 2021. doi:10.2991/efood.k.200824.002