Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context

RESEARCH ARTICLE Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context Monica Barone1, Silvia Turroni ID1*, Simone Rampelli1, Matteo Soverini1, Federica D’Amico1, Elena Biagi1, Patrizia Brigidi1, Emidio Troiani2, Marco Candela1 1 Unit of Microbial Ecology of Health, Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy, 2 Primary Care Unit and Territorial Health, Social Security Institute, Cailungo, Republic of San Marino * Abstract a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Barone M, Turroni S, Rampelli S, Soverini M, D’Amico F, Biagi E, et al. (2019) Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context. PLoS ONE 14(8): e0220619. https://doi.org/10.1371/journal. pone.0220619 Editor: Juan J. Loor, University of Illinois, UNITED STATES Received: December 21, 2018 Accepted: July 18, 2019 Published: August 8, 2019 Copyright: © 2019 Barone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data are available from MG-RAST (project ID: mgp89161). Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. The modern Paleolithic diet (MPD), featured by the consumption of vegetables, fruit, nuts, seeds, eggs, fish and lean meat, while excluding grains, dairy products, salt and refined sugar, has gained substantial public attention in recent years because of its potential multiple health benefits. However, to date little is known about the actual impact of this dietary pattern on the gut microbiome (GM) and its implications for human health. In the current scenario where Western diets, low in fiber while rich in industrialized and processed foods, are considered one of the leading causes of maladaptive GM changes along human evolution, likely contributing to the increasing incidence of chronic non-communicable diseases, we hypothesize that the MPD could modulate the Western GM towards a more “ancestral” configuration. In an attempt to shed light on this, here we profiled the GM structure of urban Italian subjects adhering to the MPD, and compared data with other urban Italians following a Mediterranean Diet (MD), as well as worldwide traditional hunter-gatherer populations from previous publications. Notwithstanding a strong geography effect on the GM structure, our results show an unexpectedly high degree of biodiversity in MPD subjects, which well approximates that of traditional populations. The GM of MPD individuals also shows some peculiarities, including a high relative abundance of bile-tolerant and fat-loving microorganisms. The consumption of plant-based foods–albeit with the exclusion of grains and pulses– along with the minimization of the intake of processed foods, both hallmarks of the MPD, could therefore contribute to partially rewild the GM but caution should be taken in adhering to this dietary pattern in the long term. Introduction In order to understand the specificities of the human microbiome assembly, extensive metaanalyses of human and non-human primate microbiomes have been recently carried out [1,2]. This comparative approach has led to the identification of several compositional changes along with a progressive reduction of biodiversity as the main distinctive features of the human gut microbiome (GM) along the evolutionary history [1]. Interestingly, these hallmarks PLOS ONE | https://doi.org/10.1371/journal.pone.0220619 August 8, 2019 1 / 14 Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context have been found to be exacerbated in Western urban populations compared to traditional and rural counterparts [3–6]. In particular, consistent with the disappearing microbiota hypothesis [7], the dramatic shrinkage of individual GM diversity in Western urban populations is deemed to depict a maladaptive microbiome state which may contribute to the rising incidence of chronic non-communicable diseases, such as obesity, diabetes, asthma and inflammatory bowel disease [8–11]. Consequently, in recent years, a large body of research has been devoted to understanding the mechanisms leading to the alterations in the Western urban GM. It is in this scenario that the multiple-hit hypothesis has been advanced [8]. According to this theory, the progressive changes in the human GM and especially the reduction of biodiversity have occurred at multiple stages along the recent transition to modern urban societies, and several aspects typical of the urbanization process—such as sanitation, antibiotics, C-section and Western diet—have been pointed out as contributing factors. In particular, the reduction in quantity and diversity of Microbiota-Accessible Carbohydrates (MACs) in the diet has been considered one of the leading causes of the disappearing GM in Western urban populations [8]. Recently defined, dietary MACs include all types of carbohydrates, coming from a variety of sources including plants, animal tissue or food-borne microbes, which—indigestible by the host—become available as an energy source for a specific GM fraction enriched in Carbohydrate Active Enzymes (CAZymes) [8,12]. Moreover, food additives, emulsifiers and xenobiotics–ubiquitous in industrially processed foods–have recently been shown as important additional drivers of GM diversity shrinkage [13]. All currently available studies exploring the disappearing GM are based on the comparison between Western urban and traditional rural populations [3–6,14–16]. Consistently, the observed GM differences are likely to be the result of the combined action of several covariates in addition to the diet–i.e. ethnicity, geographical origin, climate, subsistence, medication, hygiene and life sharing–and do not allow to weight the importance of the single determinants. In the last few years, the Modern Paleolithic Diet (MPD), with high intake of vegetables, fruit, nuts, seeds, eggs, fish and lean meat, while excluding grains, dairy products, salt and refined sugar, has attracted substantial public attention in the Western world because of its potential multiple health benefits [17–22]. In the present work, we profiled the GM structure of 15 Italian subjects following the MPD and compared it with that of 143 urban Italian individuals largely adhering to the Mediterranean Diet (MD) from our previous works [5,23]. Notwithstanding the small sample size, our GM exploratory study gave us the unique opportunity to assess to what extent the adoption of a Paleolithic dietary pattern, based on the consumption of MACs deriving from plant-based foods–but not grains–along with the exclusion of industrially processed food, may modulate the GM of Western urban popul (...truncated)