Human Gut Microbial Community Research Articles

Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented Westernized Dietary Styles on Human Gut Microbiota: A Cross Sectional Study.

Diet and lifestyle have a strong influence on gut microbiota, which in turn has important implications on a variety of health-related aspects. Despite great advances in the field, it remains unclear to which extent the composition of the gut microbiota is modulated by the intake of animal derived products, compared to a vegetable based diet. Here the specific impact of vegan, vegetarian, and omnivore feeding type on the composition of gut microbiota of 101 adults was investigated among groups homogeneous for variables known to have a role in modulating gut microbial composition such as age, anthropometric variables, ethnicity, and geographic area. The results displayed a picture where the three different dietetic profiles could be well distinguished on the basis of participant’s dietetic regimen. Regarding the gut microbiota; vegetarians had a significantly greater richness compared to omnivorous. Moreover, counts of Bacteroidetes related operational taxonomic units (OTUs) were greater in vegans and vegetarians compared to omnivores. Interestingly considering the whole bacterial community composition the three cohorts were unexpectedly similar, which is probably due to their common intake in terms of nutrients rather than food, e.g., high fat content and reduced protein and carbohydrate intake. This finding suggests that fundamental nutritional choices such as vegan, vegetarian, or omnivore do influence the microbiota but do not allow to infer conclusions on gut microbial composition, and suggested the possibility for a preferential impact of other variables, probably related to the general life style on shaping human gut microbial community in spite of dietary influence. Consequently, research were individuals are categorized on the basis of their claimed feeding types is of limited use for scientific studies, since it appears to be oversimplified.

Bioenergetic diversity of the human gut microbiome

The human microbiome has lately emerged as an important factor in health and disease. The general patterns that emerge from metagenomics studies of the microbial diversity in the human gut of healthy adults, children and infants, are that (a) the microbiome is less diverse early in life, and gets enriched after infancy, and (b) that it is dominated by organisms from two bacterial phyla: bacteroidetes and firmicutes. However, there is still considerable diversity between individuals, based on age, habitat and health status, while a lot of questions on how the diversity of the microbiome affects our health still remain unanswered. One aspect that has been largely overlooked is the diversity of the microbiome with regards to bioenergetic pathways. We therefore set out to address this by re-examining freely available data from three major studies of human gut microbiota, as deposited on MG-RAST, based on the available complete genome sequences of a set of species which represent the full bioenergetic diversity of prokaryotes across all the major bacterial and archaeal lineages. Our results indicate that a number of species are present in the human gut of both adults and infants which normally derive their energy from methanogenesis, iron oxidation, iron reduction, sulfate and arsenate reduction, and even anoxygenic photosynthesis. We discuss the meaning of the presence of these bioenergetic pathways to the dynamics of the human gut microbial community, as well as future directions to better characterize this previously unsuspected diversity.

Comparison of DNA extraction methods for human gut microbial community profiling

The human gut harbors a vast range of microbes that have significant impact on health and disease. Therefore, gut microbiome profiling holds promise for use in early diagnosis and precision medicine development. Accurate profiling of the highly complex gut microbiome requires DNA extraction methods that provide sufficient coverage of the original community as well as adequate quality and quantity. We tested nine different DNA extraction methods using three commercial kits (TianLong Stool DNA/RNA Extraction Kit (TS), QIAamp DNA Stool Mini Kit (QS), and QIAamp PowerFecal DNA Kit (QP)) with or without additional bead-beating step using manual or automated methods and compared them in terms of DNA extraction ability from human fecal sample. All methods produced DNA in sufficient concentration and quality for use in sequencing, and the samples were clustered according to the DNA extraction method. Inclusion of bead-beating step especially resulted in higher degrees of microbial diversity and had the greatest effect on gut microbiome composition. Among the samples subjected to bead-beating method, TS kit samples were more similar to QP kit samples than QS kit samples. Our results emphasize the importance of mechanical disruption step for a more comprehensive profiling of the human gut microbiome.

Gut Microbial Transformation of the Dietary Imidazoquinoxaline Mutagen MelQx Reduces Its Cytotoxic and Mutagenic Potency.

The diverse community of microbes present in the human gut has emerged as an important factor for cancer risk, potentially by altering exposure to chemical carcinogens. In the present study, human gut bacteria were tested for their capacity to transform the carcinogenic heterocyclic amine 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx). Eubacterium hallii, Lactobacillus reuteri, and Lactobacillus rossiae were able to convert MelQx to a new microbial metabolite characterized on the basis of high-resolution mass spectrometry and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2′,1′:2,3]imidazo[4,5-f]quinoxaline (MelQx-M1), resulting from conjugation with activated glycerol. Acrolein derived from the decomposition of 3-hydroxypropionaldehyde, which is the product of bacterial glycerol/diol dehydratase activity, was identified as the active compound responsible for the formation of MelQx-M1. A complex human gut microbial community obtained from invitro continuous intestinal fermentation was found to also transform MelQx to MelQx-M1. MelQx-M1 had slightly reduced cytotoxic potency toward human colon epithelial cells invitro, and diminished mutagenic potential toward bacteria after metabolic activation. As bacterially derived acrolein also transformed 2 other HCAs, namely 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3-methylimidazo[4,5-f]quinoline, these results generalize the capacity of gut microbiota to detoxify HCAs in the gut, potentially modulating cancer risk.

<b>Dynamism and diversity of human gut microbial community </b>

<b>Dynamism and diversity of human gut microbial community </b>

Evaluating the accuracy of amplicon-based microbiome computational pipelines on simulated human gut microbial communities

BackgroundMicrobiome studies commonly use 16S rRNA gene amplicon sequencing to characterize microbial communities. Errors introduced at multiple steps in this process can affect the interpretation of the data. Here we evaluate the accuracy of operational taxonomic unit (OTU) generation, taxonomic classification, alpha- and beta-diversity measures for different settings in QIIME, MOTHUR and a pplacer-based classification pipeline, using a novel software package: DECARD.ResultsIn-silico we generated 100 synthetic bacterial communities approximating human stool microbiomes to be used as a gold-standard for evaluating the colligative performance of microbiome analysis software. Our synthetic data closely matched the composition and complexity of actual healthy human stool microbiomes. Genus-level taxonomic classification was correctly done for only 50.4–74.8% of the source organisms. Miscall rates varied from 11.9 to 23.5%. Species-level classification was less successful, (6.9–18.9% correct); miscall rates were comparable to those of genus-level targets (12.5–26.2%). The degree of miscall varied by clade of organism, pipeline and specific settings used. OTU generation accuracy varied by strategy (closed, de novo or subsampling), reference database, algorithm and software implementation. Shannon diversity estimation accuracy correlated generally with OTU-generation accuracy. Beta-diversity estimates with Double Principle Coordinate Analysis (DPCoA) were more robust against errors introduced in processing than Weighted UniFrac. The settings suggested in the tutorials were among the worst performing in all outcomes tested.ConclusionsEven when using the same classification pipeline, the specific OTU-generation strategy, reference database and downstream analysis methods selection can have a dramatic effect on the accuracy of taxonomic classification, and alpha- and beta-diversity estimation. Even minor changes in settings adversely affected the accuracy of the results, bringing them far from the best-observed result. Thus, specific details of how a pipeline is used (including OTU generation strategy, reference sets, clustering algorithm and specific software implementation) should be specified in the methods section of all microbiome studies. Researchers should evaluate their chosen pipeline and settings to confirm it can adequately answer the research question rather than assuming the tutorial or standard-operating-procedure settings will be adequate or optimal.

The Effect of Probiotics, Antibiotics, and Antipyretic Analgesics on Gut Microbiota Modification

Human gut microbial community is playing a critical role in human health and associated with different human disease. In parallel, probiotics, antibiotics, and antipyretic analgesics (AAs) were developed to improve human health or cure human diseases. We therefore examined how probiotics, antibiotics, and AAs influence to the gut microbiota. Three independent case/control studies were designed from the cross-sectional cohort data of 1,463 healthy Koreans. The composition of the gut microbiota in each case and control group was determined via 16S ribosomal RNA Illumina next-generation sequencing. The correlation between microbial taxa and the consumption of each drug was tested using zero-inflated Gaussian mixture models, with covariate adjustment of age, sex, and body mass index (BMI). Probiotics, antibiotics, and AAs consumption yielded the significant differences in the gut microbiota, represented the lower abundance of Megasphaera in probiotics, the higher abundance of Fusobacteria in antibiotics, and the higher abundance of Butyrivibrio and Verrucomicrobia in AAs, compared to each control group. The reduction of Erysipelotrichaceae family was common in three drugs consumption.

Bioenergetic diversity of the human gut microbiome

Abstract The human microbiome has lately emerged as an important factor in health and disease. The general patterns that emerge from metagenomics studies of the microbial diversity in the human gut of healthy adults, children and infants, are that (a) the microbiome is less diverse early in life, and gets enriched after infancy, and (b) that it is dominated by organisms from two bacterial phyla: bacteroidetes and firmicutes. However, there is still considerable diversity between individuals, based on age, habitat and health status, while a lot of questions on how the diversity of the microbiome affects our health still remain unanswered. One aspect that has been largely overlooked is the diversity of the microbiome with regards to bioenergetic pathways. We therefore set out to address this by re-examining freely available data from three major studies of human gut microbiota, as deposited on MG-RAST, based on the available complete genome sequences of a set of species which represent the full bioenergetic diversity of prokaryotes across all the major bacterial and archaeal lineages. Our results indicate that a number of species are present in the human gut of both adults and infants which normally derive their energy from methanogenesis, iron oxidation, iron reduction, sulfate and arsenate reduction, and even anoxygenic photosynthesis. We discuss the meaning of the presence of these bioenergetic pathways to the dynamics of the human gut microbial community, as well as future directions to better characterize this previously unsuspected diversity.

Abstract P255: Gut Microbiota Diversity and Specific Microbial Genera Associate with Cardiovascular Disease Risk: Findings From the Bogalusa Heart Study

Recent advances in sequencing technology have made it feasible to characterize human gut microbial communities (or microbiota) and examine their associations with disease outcomes, including cardiovascular disease (CVD) related traits. However, there is a paucity of research examining how the human gut microbiome may influence overall CVD risk in population based studies. The objective of the current study was to identify composite measures of microbiota diversity and specific microbial genera that associate with CVD risk among participants of the Bogalusa Heart Study (BHS). The current BHS cohort includes 1,257 participants who have been screened at least two times in childhood and two times in adulthood for CVD risk factors. For the microbiome study, we selected the 55 participants at highest CVD risk and 57 participants at lowest CVD risk using a z-score based data reduction technique, leveraging longitudinal mean measures of systolic BP, low-density lipoprotein cholesterol, and fasting plasma glucose levels. Next generation 16S rRNA sequencing of the V4 hypervariable region was conducted using genomic bacterial DNA extracted from stool samples of the 112 participants. The Wilcoxon rank sum test was used to examine differences in measures of alpha diversity, including observed operational taxonomic units (OTUs) and the Chao1 index, along with specific microbial taxa between CVD risk groups. Permutation multivariate analysis of variance (PERMANOVA) was used to test compositional differences based on unweighted Unifrac distance as a measure of beta diversity. We observed significantly less alpha diversity in those at high versus those at low CVD risk (P=0.04 and 0.02 for observed OTU and Chao1 index measures, respectively). The PERMANOVA test indicated marginal significance of compositional differences between the two groups (P=0.07). In addition, 10 microbial genera significantly differed between high and low CVD risk participants, including Faecalibacterium (P=0.0014), Subdoligranulum (P=0.01), Turicibacter (P=0.01), Rothia (P=0.01), Lachnospira (P=0.01), Haemophilus (P=0.03), Dialister (P=0.03), Bifidobacterium (P=0.03), Oscillibacter (P=0.04), and Megamonas (P=0.05). In summary, we provide empirical evidence of lower microbial enrichment among BHS participants at high versus those at low CVD risk, along with promising findings of differences in specific microbial genera between CVD risk groups.

Modulation of the human gut microbiota by dietary fibres occurs at the species level.

BackgroundDietary intake of specific non-digestible carbohydrates (including prebiotics) is increasingly seen as a highly effective approach for manipulating the composition and activities of the human gut microbiota to benefit health. Nevertheless, surprisingly little is known about the global response of the microbial community to particular carbohydrates. Recent in vivo dietary studies have demonstrated that the species composition of the human faecal microbiota is influenced by dietary intake. There is now potential to gain insights into the mechanisms involved by using in vitro systems that produce highly controlled conditions of pH and substrate supply.ResultsWe supplied two alternative non-digestible polysaccharides as energy sources to three different human gut microbial communities in anaerobic, pH-controlled continuous-flow fermentors. Community analysis showed that supply of apple pectin or inulin resulted in the highly specific enrichment of particular bacterial operational taxonomic units (OTUs; based on 16S rRNA gene sequences). Of the eight most abundant Bacteroides OTUs detected, two were promoted specifically by inulin and six by pectin. Among the Firmicutes, Eubacterium eligens in particular was strongly promoted by pectin, while several species were stimulated by inulin. Responses were influenced by pH, which was stepped up, and down, between 5.5, 6.0, 6.4 and 6.9 in parallel vessels within each experiment. In particular, several experiments involving downshifts to pH 5.5 resulted in Faecalibacterium prausnitzii replacing Bacteroides spp. as the dominant sequences observed. Community diversity was greater in the pectin-fed than in the inulin-fed fermentors, presumably reflecting the differing complexity of the two substrates.ConclusionsWe have shown that particular non-digestible dietary carbohydrates have enormous potential for modifying the gut microbiota, but these modifications occur at the level of individual strains and species and are not easily predicted a priori. Furthermore, the gut environment, especially pH, plays a key role in determining the outcome of interspecies competition. This makes it crucial to put greater effort into identifying the range of bacteria that may be stimulated by a given prebiotic approach. Both for reasons of efficacy and of safety, the development of prebiotics intended to benefit human health has to take account of the highly individual species profiles that may result.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0224-3) contains supplementary material, which is available to authorized users.

Intrinsic association between diet and the gut microbiome: current evidence.

The gut microbiome performs many crucial functions for the human host, but the molecular mechanisms by which host, microbe and diet interact to mediate health and disease are only starting to be revealed. Here we review the literature on how changes in the diet affect the microbiome. A number of studies have shown that within a geographic region, different diets (such as vegan vs. omnivore) are associated with differences in a modest number of taxa but do not reliably produce radical differences within the gut microbial community. In contrast, studies that look across continents consistently find profoundly different microbial communities between Westernized and traditional populations, although it remains unclear to what extent diet or other differences in lifestyle drive these distinct microbial community structures. Furthermore, studies that place subjects on controlled short term experimental diets have found the resulting alterations to the gut microbial community to generally be small in scope, with changes that do not overcome initial individual differences in microbial community structure. These results emphasize that the human gut microbial community is relatively stable over time. In contrast, short term changes in diet can cause large changes in metabolite profiles, including metabolites processed by the gut microbial community. These results suggest that commensal gut microbes have a great deal of genetic plasticity and can activate different metabolic pathways independent of changes to microbial community composition. Thus, future studies of the how diet impacts host health via the microbiome may wish to focus on functional assays such as transcriptomics and metabolomics, in addition to 16S rRNA and whole-genome metagenome shotgun analyses of DNA. Taken together, the literature is most consistent with a model in which the composition of the adult gut microbial community undergoes modest compositional changes in response to altered diet but can nonetheless respond very rapidly to dietary changes via up- or down-regulation of metabolic pathways that can have profound and immediate consequences for host health.

Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria.

ABSTRACTElucidation of the molecular mechanisms underlying the human gut microbiota’s effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective.

Microbiome Resilience during Inflammation

Human gut microbial communities are subject to numerous perturbations, including dietary changes, exposures to antibiotics and toxins, and pathogen infection. We are developing genetic tools to identify and characterize the mechanisms these microbes use to persist in the perturbed gut environment. Our results suggest that single genes can determine the resilience of commensal bacteria during inflammation. Such factors may provide important insights into the dynamics of recurrent pathogen infection and efforts to introduce stable beneficial microbes into the gut.

Glycan degradation (GlyDeR) analysis predicts mammalian gut microbiota abundance and host diet-specific adaptations.

ABSTRACTGlycans form the primary nutritional source for microbes in the human gut, and understanding their metabolism is a critical yet understudied aspect of microbiome research. Here, we present a novel computational pipeline for modeling glycan degradation (GlyDeR) which predicts the glycan degradation potency of 10,000 reference glycans based on either genomic or metagenomic data. We first validated GlyDeR by comparing degradation profiles for genomes in the Human Microbiome Project against KEGG reaction annotations. Next, we applied GlyDeR to the analysis of human and mammalian gut microbial communities, which revealed that the glycan degradation potential of a community is strongly linked to host diet and can be used to predict diet with higher accuracy than sequence data alone. Finally, we show that a microbe’s glycan degradation potential is significantly correlated (R = 0.46) with its abundance, with even higher correlations for potential pathogens such as the class Clostridia (R = 0.76). GlyDeR therefore represents an important tool for advancing our understanding of bacterial metabolism in the gut and for the future development of more effective prebiotics for microbial community manipulation.

Colonizing the Embryonic Zebrafish Gut with Anaerobic Bacteria Derived from the Human Gastrointestinal Tract

The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

Crystal ball – 2013

Crystal ball – 2013

Abstract IA15: The microbiome and its association with human metabolism and adiposity.

Abstract The rise in obesity and inflammation-based disease is striking across all socioeconomic levels at alarming rates. Over the past 30 years in the U.S., adults and children have experienced a marked increase in the prevalence of overweight and obesity. Two-thirds of American adults are obese or overweight. Among adults aged 20-74 years, the prevalence of obesity increased from 15.0% to 32.9%. Obesity-related disease risk has also been on the rise although there is some variation among individuals. Environmental and host genetic factors may account for some of the variation in disease risk seen among individuals. Recently, the human gut microbial community (GMC) has been identified as a possible factor that may alter host metabolism and adiposity. The Human Microbiome Project, a part of NIH's recent Roadmap for Medical Research, opened new avenues to study the gut microbiome (i.e., all the microbial genomes and their genes) as a modifiable environmental factor that influences human health. New molecular methods, that do not require culturing bacteria, have uncovered high within- and between-individual gut microbial diversity. The highly diverse gut microbiome contains many metabolic pathways that alter dietary constituents and affect human health in both positive and negative ways. Thus, inter-individual variation in disease risk may be, in part, associated with the gut microbiome. The GMC is tightly associated with host energy metabolism and provides a mechanistic link between human health and exposures. Energy use and adiposity are influenced by a tight and coordinated connection between dietary intake, the GMC, and the host. The metabolism of diet by the microbiome is complex and is associated with the metabolic capability of specific bacterial members in the gut community often arranged in consortia or networks of micro-organisms. The recent characterization of bacterial enterotypes, based on molecular analyses of the GMC, suggests that networks of microbial species have redundant metabolic pathways which provide about 10% of the host nutrition by the metabolism of diet. For example, the gut microbiome alters energy storage through the metabolism of dietary carbohydrates to short chain fatty acids (SCFA). In turn, the SCFA from bacterial metabolism influence pathways of carbon metabolism and fat storage in the human host. Mechanisms by which the gut microbiome influences human metabolism and subsequent disease risk include: regulation of energy uptake from diet, interaction with signaling molecules involved in host metabolism, modification of gut permeability, and sub-chronic inflammation, a hallmark of obesity-related diseases. In addition, recent studies in humans and mice suggest that the host genotype may exert some control on the composition of the gut microbiome and attenuate obesity-related diseases. These pathways give insight into the multiple ways through which the gut microbiome may influence adiposity and disease risk. Citation Format: Meredith A. J. Hullar. The microbiome and its association with human metabolism and adiposity. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA15.

Multidomain Carbohydrate-binding Proteins Involved in Bacteroides thetaiotaomicron Starch Metabolism

Human colonic bacteria are necessary for the digestion of many dietary polysaccharides. The intestinal symbiont Bacteroides thetaiotaomicron uses five outer membrane proteins to bind and degrade starch. Here, we report the x-ray crystallographic structures of SusE and SusF, two outer membrane proteins composed of tandem starch specific carbohydrate-binding modules (CBMs) with no enzymatic activity. Examination of the two CBMs in SusE and three CBMs in SusF reveals subtle differences in the way each binds starch and is reflected in their K(d) values for both high molecular weight starch and small maltooligosaccharides. Thus, each site seems to have a unique starch preference that may enable these proteins to interact with different regions of starch or its breakdown products. Proteins similar to SusE and SusF are encoded in many other polysaccharide utilization loci that are possessed by human gut bacteria in the phylum Bacteroidetes. Thus, these proteins are likely to play an important role in carbohydrate metabolism in these abundant symbiotic species. Understanding structural changes that diversify and adapt related proteins in the human gut microbial community will be critical to understanding the detailed mechanistic roles that they perform in the complex digestive ecosystem.

Comparative evaluation of establishing a human gut microbial community within rodent models

The structure of the human gut microbial community is determined by host genetics and environmental factors, where alterations in its structure have been associated with the onset of different diseases. Establishing a defined human gut microbial community within inbred rodent models provides a means to study microbial-related pathologies, however, an in-depth comparison of the established human gut microbiota in the different models is lacking. We compared the efficiency of establishing the bacterial component of a defined human microbial community within germ-free (GF) rats, GF mice and antibiotic-treated specific pathogen-free mice. Remarkable differences were observed between the different rodent models. While the majority of abundant human-donor bacterial phylotypes were established in the GF rats, only a subset was present in the GF mice. Despite the fact that members of the phylum Bacteriodetes were well established in all rodent models, mice enriched for phylotypes related to species of Bacteroides. In contrary to the efficiency of Clostridiales to populate the GF rat in relative proportions to that of the human-donor, members of Clostridia cluster IV only poorly colonize the mouse gut. Thus, the genetic background of the different recipient rodent systems (that is, rats and mice) strongly influences the nature of the populating human gut microbiota, determining each model’s biological suitability.

Dairy Products and Cancer

Cancer is a group of more than 100 diseases in which cells display uncontrolled growth, invasion, and sometimes metastasis. Milk and dairy products contain micronutrients and several bioactive constituents that may influence cancer risk and progression. Much of the focus of human, population-based studies has been on the effects of intake of milk and total dairy products or of calcium intake. Based on a systematic review of the epidemiologic literature, the World Cancer Research Fund and American Institute for Cancer Research report concluded there was a probable association between milk intake and lower risk of colorectal cancer, a probable association between diets high in calcium and increased risk of prostate cancer, and limited evidence of an association between milk intake and lower risk of bladder cancer. For other cancers, the evidence was mixed or lacking. Since the 2007 report, several additional, large-cohort studies have been published, including two that show an inverse association between intake of cultured dairy products and bladder cancer. Little is known about the potential effect of various bioactives produced during rumen microbe metabolism on cancer risk. Furthermore, studies support a role of live microbes present in some dairy products in the modulation of the human gut microbial community and gut metabolism. Given the growing appreciation for the role of the gut microbial community in relation to immune function and health and disease, including cancer, the potential role of various dairy products in the modulation of the human gut microbiome warrants further evaluation.Key teaching points: • As a dietary exposure, dairy products are a complex group of foods and composition varies by region, which makes evaluation of their association with disease risk difficult.• For most cancers, associations between cancer risk and intake of milk and dairy products have been examined only in a small number of cohort studies, and data are inconsistent or lacking.• Meta-analyses of cohort data available to date support an inverse association between milk intake and risk of colorectal and bladder cancer and a positive association between diets high in calcium and risk of prostate cancer.• Other constituents of dairy products, such as rumen-derived metabolites, have not been evaluated extensively for cancer-preventive properties.• The influence of live microbes in fermented dairy products and certain cheeses on the human gut microbiome and immune function is a growing area of study.