Influences of Helicobacter pylori infection on diversity, heterogeneity, and composition of human gastric microbiomes across stages of gastric cancer development.

BACKGROUND: About a half of the world's population is infected with Helicobacter pylori (H. pylori), but only 1%-3% of them develop gastric cancer. As a primary risk factor for gastric cancer, the relationship between H. pylori infection and gastric microbiome has been a focus in recent years. MATERIALS AND METHODS: We reanalyze 11 human gastric microbiome datasets with or without H. pylori, covering the healthy control (HC) and four disease stages (chronic gastritis (CG), atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC)) of gastric cancer development to quantitatively compare the influences of the H. pylori infection and disease stages on the diversity, heterogeneity, and composition of gastric microbiome. Four medical ecology approaches including (i) diversity analysis with Hill numbers, (ii) heterogeneity analysis with Taylor's power law extensions (TPLE), (iii) diversity scaling analysis with diversity-area relationship (DAR) model, and (iv) shared species analysis were applied to fulfill the data reanalysis. RESULTS: (i) The influences of H. pylori infection on the species diversity, spatial heterogeneity, and potential diversity of gastric microbiome seem to be more prevalent than the influences of disease stages during gastric cancer development. (ii) The influences of H. pyloriinfection on diversity, heterogeneity, and composition of gastric microbiomes in HC, CG, IM, and GC stages appear more prevalent than those in AG stage. CONCLUSION: Our study confirmed the impact of H. pylori infection on human gastric microbiomes: The influences of H. pylori infection on the diversity, heterogeneity, and composition of gastric microbiomes appear to be disease-stage dependent.

Diversity Scaling Analysis of Chinese Gut Microbiomes Across Ethnicities and Lifestyles.

Diversity scaling (changes) of human gut microbiome is important because it measures the inter-individual heterogeneity of diversity and other important parameters of population-level diversity. Understanding the heterogeneity of microbial diversity can be used as a reference for the personalized medicine of microbiome-associated diseases. Similar to diversity per se, diversity scaling may also be influenced by host factors, especially lifestyles and ethnicities. Nevertheless, this important topic regarding Chinese populations has not been addressed, to our best knowledge. Here, we fill the gap by applying a recent extension to the classic species-area relationship (SAR), i.e., diversity-area relationship (DAR), to reanalyze a large dataset of Chinese gut microbiomes covering the seven biggest Chinese ethnic groups (covering > 95% Chinese) living rural and urban lifestyles. Four DAR profiles were constructed to investigate the diversity scaling, diversity overlap, potential maximal diversity, and the ratio of local to global diversity of Chinese gut microbiomes. We discovered the following: (i) The diversity scaling parameters (z) at various taxon levels are little affected by either ethnicity or lifestyles, as exhibited by less than 0.5% differences in pairwise comparisons. (ii) The maximal accrual diversity (potential diversity) exhibited difference in only about 5% of pairwise comparisons, and all of the differences occurred in ethnicity comparisons (i.e., lifestyles had no effects). (iii) Ethnicity seems to have stronger effects than lifestyles across all taxon levels, and this may reflect the reality that China has been experiencing rapid urbanization in the last few decades, while the ethnic-related genetic background may change relatively little during the same period.

Inter-Individual Diversity Scaling Analysis of the Human Virome With Classic Diversity-Area Relationship (DAR) Modeling.

The human virome is a critical component of the human microbiome, and it is believed to hold the richest diversity within human microbiomes. Yet, the inter-individual scaling (changes) of the human virome has not been formally investigated to the best of our knowledge. Here we fill the gap by applying diversity-area relationship (DAR) modeling (a recent extension to the classic species-area law in biodiversity and biogeography research) for analyzing four large datasets of the human virome with three DAR profiles: DAR scaling (z)-measuring the inter-individual heterogeneity in virome diversity, MAD (maximal accrual diversity: D max ) and LGD ratio (ratio of local diversity to global diversity)-measuring the percentage of individual to population level diversity. Our analyses suggest: (i) The diversity scaling parameter (z) is rather resilient against the diseases as indicated by the lack of significant differences between the healthy and diseased treatments. (ii) The potential maximal accrual diversity (D max ) is less resilient and may vary between the healthy and diseased groups or between different body sites. (iii) The LGD ratio of bacterial communities is much smaller than for viral communities, and relates to the comparatively greater heterogeneity between local vs. global diversity levels found for bacterial-biomes.

Does Ulcerative Colitis Influence the Inter-individual Heterogeneity of the Human Intestinal Mucosal Microbiome?

The dysbiosis of the gut microbiome associated with ulcerative colitis (UC) has been extensively studied in recent years. However, the question of whether UC influences the spatial heterogeneity of the human gut mucosal microbiome has not been addressed. Spatial heterogeneity (specifically, the inter-individual heterogeneity in microbial species abundances) is one of the most important characterizations at both population and community scales, and can be assessed and interpreted by Taylor's power law (TPL) and its community-scale extensions (TPLEs). Due to the high mobility of microbes, it is difficult to investigate their spatial heterogeneity explicitly; however, TPLE offers an effective approach to implicitly analyze the microbial communities. Here, we investigated the influence of UC on the spatial heterogeneity of the gut microbiome with intestinal mucosal microbiome samples collected from 28 UC patients and healthy controls. Specifically, we applied Type-I TPLE for measuring community spatial heterogeneity and Type-III TPLE for measuring mixed-species population heterogeneity to evaluate the heterogeneity changes of the mucosal microbiome induced by UC at both the community and species scales. We further used permutation test to determine the possible differences between UC patients and healthy controls in heterogeneity scaling parameters. Results showed that UC did not significantly influence gut mucosal microbiome heterogeneity at either the community or mixed-species levels. These findings demonstrated significant resilience of the human gut microbiome and confirmed a prediction of TPLE: that the inter-subject heterogeneity scaling parameter of the gut microbiome is an intrinsic property to humans, invariant with UC disease.