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Personalized dietary intervention as a complementary strategy to modify gut microbiome signature and improve immunotherapy outcomes in cancer patients
* 1, 2 , * 1, 3 , 4 , 5 , 6 , 6 , 6
1  Department of Clinical Pharmacology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia
2  University of Rijeka Faculty of Health Studies, Ul. Viktora cara Emina 5, 51000 Rijeka, Croatia
3  Department of Basic and Clinical Pharmacology with Toxicology, University of Rijeka, Faculty of Medicine, Braće Branchetta 20, 51000 Rijeka, Croatia
4  Department of Health Ecology, Teaching Institute of Public Health of Primorsko-goranska County, Krešimirova 52a, 51000 Rijeka, Croatia
5  Department of Radiotherapy and Oncology, Clinical Hospital Centre Rijeka, Krešimirova 42, 51000 Rijeka, Croatia
6  Department of Oncology, University Hospital Centre Zagreb, Ulica Mije Kišpatića 12, 10000 Zagreb, Croatia
Academic Editor: Maria-Luz Fernandez


Not all cancer patients respond to immunotherapy, and the variation in response may be attributed to the individual's microbiome, which is profoundly influenced by dietary habits. Understanding and manipulating the microbiome through dietary interventions offer a potential avenue for enhancing immunotherapy outcomes in cancer patients and consequently may serve as a complementary therapeutic strategy.
Bearing in mind the latter as well as our previous research the importance of gut microbiome as a co-denominator for immunotherapy response, and aiming towards constructing a protocol on dietary intervention for enhancing immunotherapy response in metastatic melanoma patients, we performed a systematic review according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 2130 citations were identified through searching PubMed/Medline using the following search strategy: ((food) OR (diet*) OR (nutri*)) AND (immunother*) AND ((butyrate) OR (SCFA) OR (microbio*)) AND (cancer). Animal studies, studies with participants younger than 18, review articles, case reports, book chapters and publications before 2015 were not within our scope. Since any relevant investigational studies were not identified, we proceeded with exploring diet-microbiome-immunotherapy axis through hand-searching and analyzing the secondary/indirect evidence.
Different dietary habits can influence the abundance and diversity of microorganisms within the gut. A diet with moderately elevated sodium use (2.3-4 g per day) diet rich in fiber (>25 g daily), fruits and vegetables (≥5 servings daily), and whole grains (≥3 servings daily) has been associated with a more diverse and beneficial microbiome, which in turn promotes the production of short-chain fatty acids (SCFA). On the other hand, a diet high in processed foods, sugars, and saturated fatty acids may lead to a less diverse and potentially less favorable microbiome.
A scarce body of literature, discussing on the intricate interplay between the microbiome and immune system, suggests that specific microbiome signatures producing essential metabolites such as SCFAs may enhance the effectiveness of immunotherapy. To elaborate, SCFAs can regulate the activity of immune cells not only by triggering metabolic and epigenetic reprogramming but also by binding to cognate receptors on the surface of cells.
Thus, profound understanding of the complex relationship between diet, SCFAs, and immunotherapy response holds great promise for developing personalized dietary approaches to cancer immunotherapy-containing treatment regimens. To deduce, by elucidating the mechanisms involved and identifying concrete personalized dietary strategies that optimize gut microbiome and SCFA production, it may be possible to further enhance the effectiveness of immunotherapy, offer novel therapeutic approaches for cancer patients, and improve their quality of life.

Keywords: dietary intervention; immunotherapy; microbiome; short-chain fatty acids