A Nutritional Anthropology of the Human Gut Microbiota

Carlotta De Filippo and Kieran M. Tuohy,    Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all’Adige, Trento, Italy

Undoubtedly, modern humankind is an omnivorous species. Nevertheless, types of diet changed radically over the course of human evolution, from hunter–gatherers, through the birth of agriculture and culminating with the modern Western-style diet. The Upper Paleolithic period is the crucial time because of the appearance of anatomically modern humans in Europe.

The human gut “metagenome” is a complex consortium of trillions of microbes, whose collective genomes contain at least 100-times as many genes as our own eukaryote genome. This essential “organ” provides the host with enhanced metabolic capabilities, protection against pathogens, education of the immune system and modulation of gastrointestinal development.

Historically, the microbial ecosystem of the gastrointestinal tract was specific for an environmental niche, as much as the flora and fauna of an ecosystem are geographically distinct. A clear example of this richness and diversity is that currently in Africa, the microbial composition is very different from that described in the Western world. Globalization of the microbial population of our digestive tracts is due to industrialization and standardization of food chain products that homogenizes the microorganisms that we ingest. Understanding the evolution of human–microbe ecosystems greatly benefits from a baseline reflecting an ancestral state of the human microbiome. The study of our closest living cousins, the other great apes, provides one path to reconstruct ancestral microbiomes. Retrieving human microbiome information from samples left behind by our distant ancestors would provide an ideal approach to understanding the coevolution of humans and microbes.

Keywords

Gut microbiota; Metagenomics; Diet; Microbial communities

Human Diet or Microbiota, Which Came First?

The feeding strategy of Homo sapiens appears to be characterized by an extraordinary omnivorism, which has no equal among mammals with the exception to some extent of the Suidae and the brown bear. This strategy allows him to have a diet that is able to capture all substances and nutrients necessary for its energy and structural needs, according to the best sources, such as foods, available in the ecosystem of origin and from a certain point in its evolution, adapted to remote ecosystems. We can therefore say that diet is one of the main factors that differentiates and drives evolution of human populations. Dietary differences originated from cultural evolution and geographic differences in availability of crops and cultivation and animal husbandry. It is widely recognized that a varied and balanced diet is essential to an individual’s health. The adverse effects of nutrient deficiency are numerous and well documented.1–4 Because nutritionally related problems continue to be the cause behind many diseases that hinder progress towards universally adequate health, all countries should be actively pursuing the improvement of their people’s nutritional status. Recently we witnessed an explosion of food consumption studies in both urban and rural areas of developing countries.5–7 These types of studies are vital to our understanding of more “transitional” and/or “traditional” diets vs. the modern-day Western-style diet. Furthermore, food-consumption in rural communities in particular generally involves a large proportion of the food coming from home-production or gathering or, at the very least, having been grown, produced and purchased locally. Therefore, diets are usually monotonous and simple because they are dependent on the availability of foods in the home or local markets as well as the prices of those foods. However, the foods themselves, often consumed with little processing or using traditional fermentation technologies, represent complex mixtures of non-digestible carbohydrates and fibers, polyphenols and live fermentative microorganisms, thereby representing both complex nutritional support for the gut microbiota and an important source of passenger microorganisms with immune-modulatory and metabolic potential. The relative invariability of these traditional diets may potentially be reflected in gut colonization by relatively homogeneous and characteristic microbiomes. Recent discoveries highlighting the importance of gut microbiota have demonstrated how the availability of the nutrients present in the foods comprising everyone’s diet is highly dependent on the human gut microbiota. The question then becomes, to what extent is the human gut microbiota dependent on changes in diet and how robust is the human microbiota from birth to death? To propose potential answers to these questions first of all we have to understand what is the human microbiota.

Metagenomics and Cultivation-Independent Assessment of Human Gut Microbiota

The human gut microbiota is composed of commensal microorganisms inherited largely from our mothers at birth, passengers’ microorganisms, mainly environmental, with which we come into continuous contact via the food we eat, and potential pathogens, exogenous invaders which try to overcome the body’s defenses and cause disease. In the 20th century our knowledge of the human microbiota was constrained by the ability to describe and study the biological functions of less than a hundred cultivable bacteria. The species we described until the year 2000 were also the most easily cultivated, and given the special attention of funding agencies towards pathogens, we fundamentally ignored the genome to function relation for the vast majority of our commensal organisms which do not cause disease and a handful of bacterial species used in food production and shown to dominate the gut microbiota of breast-fed infants, the lactobacilli and bifidobacteria, respectively.

Furthermore, for a century the study of microorganisms has been limited by the ability to cultivate them. The established view is that only a subset of the microbial species which make up our microbiome can be easily cultivated. Recently, the scientific revolution driven by high-throughput sequencing techniques (Next Generation Sequencing, NGS), has made possible the unraveling of the evolutionary history of human gut microbiome. Key to this endeavor has been the emergence of bioinformatics tools necessary to describe the microbial ecology-encoded high-resolution NGS data derived from diverse microbiomes.

Large-scale projects such as the European Metagenomics of the Human Intestinal Tract MetaHIT8 and the US Human Microbiome Project, HMP9,10 have made substantial progress towards this goal and the amount of metagenomic information is exponentially increasing, especially that obtained for individuals living in industrialized countries. The first EU-funded MetaHIT consortium produced Illumina sequences of fecal samples of 124 European individuals, including healthy, overweight and obese adults, as well as patients with inflammatory bowel disease (IBD).8 When extended to Japanese and American populations, MetaHIT also established that the worldwide population could be classified into three distinct enterotypes.11 The NIH-funded Human Microbiome Project, HMP Consortium, is also developing and indexing another fundamental reference set of microbial genome sequences from a population of 242 healthy adults, sampled at different body sites, generating 5177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far.9,10 In parallel, they have sequenced approximately 800 reference strains isolated from the human body, generating data that represent the largest resource describing the abundance and variety of the human microbiome. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome.9,10 The information deposited in these resources promises to be a goldmine for pathway and network inference, reconstructing the super-meta-pathway subtending the interaction between humans and their microbiomes.

Microbiome and Human Nutritional Phenotype

The role of the gut microbiota in provision of nutritionally relevant molecules for human health and nutrition is still largely unknown, but indeed these organisms do contribute metabolic and digestive functions absent from the human genome.12 A glimpse of the metabolic pathway complexity contained in metagenomics datasets first emerged from the study of Gill et al.13: the human genome lacks most of the enzymes required for degradation of plant polysaccharides and they are supplied by the human gut microbiome which can metabolize cellulose, starch and unusual sugars such as arabinose, mannose, and xylose, thanks to at least 81 different glycoside hydrolase families. With the aim of understanding the dietary modulation of gut microbiota, Zhu et al.14 undertook a large-scale analysis of 16S rRNA gene sequences to profile the microbiota inhabiting the digestive system of giant pandas using a metagenomic approach. They performed predicted gene functional classification, finding the presence of putative cellulose-metabolizing symbionts in this little-studied microbial environment, explaining how giant pandas are able to partially digest bamboo fiber, despite a genome lacking enzymes that can degrade cellulose. This study showed the...