Impact of Different Types of Diet on Gut Microbiota Profiles and Cancer Prevention and Treatment

March 2019
Rainer J. Klement and Valerio Pazienza

Abstract

Diet is frequently considered as a food regimen focused on weight loss, while it is actually the sum of food consumed by the organism. Western diets, modern lifestyle, sedentary behaviors, smoking habits, and drug consumption have led to a significant reduction of gut microbial diversity, which is linked to many non-communicable diseases (NCDs).

The latter kill 40 million people each year, equivalent to more than 70% of all deaths globally. Among NCDs, tumors play a major role, being responsible for 29% of deaths from NCDs.

A link between diet, microbiota, and cancer prevention and treatment has recently been unveiled, underlining the importance of a new food culture based on limiting dietary surplus and on preferring healthier foods.

Here, we review the effects of some of the most popular “cancer-specific” diets on microbiota composition and their potential impact on cancer prevention and treatment.

Paleolithic Diet, Microbiota, and Cancer

Evolutionary medicine provides a framework for a common explanation of the increase of NCDs, according to which an insufficient adaption to the modern lifestyle leads to disease. Diet plays a key role within this framework, and the term “Paleolithic diet” or “Paleo diet”, (PD) has been introduced to refer to a modern diet mimicking the diet of our ancestors during the Old Stone Age, which chronologically spans the majority of human existence [60].

The modern PD typically consists of the following patterns: (a) High consumption of fruits, herbs, spices, and vegetables; (b) Moderate-to-high consumption of lean meats, organs, fish, and eggs; (c) Moderate consumption of nuts and seeds; (d) Exclusion of all processed foods, legumes, grains, dairy products, and plant oils (except for olive and coconut oil) and, in some PD variants, also of nightshades. It is the latter characteristic (d) that distinguishes the PD from most other diets and could be part of an explanation for the superiority of a PD over other “healthy” diets (including the MD) in small randomized trials [61,62]; in particular, grains and legumes have been causally associated with the disruption of intestinal barrier integrity and the promotion of auto-immune and inflammatory NCDs, including cancer and obesity [61,63,64]. Indeed, several protocols for treating auto-immune diseases exist, which are based on PD eating patterns, focusing on the elimination of several food groups typical of the Western diet [65,66].

A PD also ensures a high consumption of microbiota-accessible carbohydrates, which is predicted to optimize gut microbial diversity [67]. In fact, the microbiome of the Tanzanian Hadza hunter–gatherers, who still consume a diet mostly composed of foods that would have been available to early humans during the Paleolithic era in Africa, has been shown to be much more diverse than that of urban Italians, with Firmicutes (72 ± 1.9%) and Bacteroidetes (17 ± 1.1%) dominating on the phylum level, followed by Proteobacteria (6 ± 1.2%) and Spirochaetes (3 ± 0.9%), which were relatively enriched compared to Italians [68].

However, the evolutionary perspective would also entail that the Hadza microbiome is optimized for their lifestyle as equatorial hunter–gatherers, while the “optimal” ancestral microbiome of Europeans or other populations further away from the equator would be different, because non-equatorial hunter–gatherer diets are lower in carbohydrate and fiber [69].

A very recent study investigated healthy Italians following a modern PD for more than one year. The dominating phyla of the gut microbiome were Firmicutes (65.1 ± 2.1%) and Bacteroidetes (24.6 ± 2.2%), followed by Proteobacteria (4.4 ± 1.6%), Actinobacteria (3.4 ± 0.8%), and Verrucomicrobia (1.2 ± 0.5%). At the family level, the dominant bacteria were Ruminococcaceae, Lachnospiraceae, Bacteroidaceae, and Prevotellaceae, while, at the genus level, Bacteroides, Pervotella, and Faecalibacterium dominated [70].

Compared to Italians adhering to the MD, the PD microbiome diversity was much higher and comparable to that of the Hadza hunter–gatherers. This study is important in showing that the loss of microbiome diversity in Western societies can be counteracted by returning to a modern PD composed of natural (also region-specific) foods but without dairy, grains, refined sugar, and other processed foods.

The association with high microbiome diversity and their putatively anti-inflammatory properties would make PDs interesting to investigate in future clinical studies as adjuncts to cancer therapy. Recently, a Hungarian group published several case reports of a ketogenic version of a PD appearing therapeutic against tumor growth [71,72,73], demonstrating the potential of this approach.

Conclusions

The dietary patterns discussed in this review are emerging to be potentially effective for preventing cancer and increasing the overall health of individuals. These effects are mediated, at least in part, by the promotion of an eubiotic microbiome.

There is also evidence that such dietary modulation of the microbiota could have synergistic effects during cancer therapy, although it has to be acknowledged that most research in this area so far relies on mouse models whose microbiota, although similar at the phylum level, are slightly different at lower taxonomic levels.

Clinical studies are therefore needed to confirm the role of microbiota modulation in cancer treatment, as suggested by these animal data. Nevertheless, the diffusion of the “fast food culture” in industrialized countries and its hallmark, the Western diet, which is low in fiber and rich in sugar and processed foods, are tightly linked to a loss of microbial diversity, dysbiosis, and a high risk of obesity, cardiovascular diseases, metabolic syndrome, and cancer.

While eubiosis may heavily depend on the environment of an individual and may therefore be hard to characterize in terms of general microbial composition, there is strong evidence that individual microbiomes would benefit from efforts towards spreading and recommending a new food culture based on limiting dietary surplus and on preferring natural, regional, and fresh foods.