Host genetics exerts lifelong effects upon hindgut microbiota and its association with bovine growth and immunity

AbstractThe gut microbiota is a complex ecological community that plays multiple critical roles within a host. Known intrinsic and extrinsic factors affect gut microbiota structure, but the influence of host genetics is understudied. To investigate the role of host genetics upon the gut microbiota structure, we performed a longitudinal study in which we evaluated the hindgut microbiota and its association with animal growth and immunity across life. We evaluated three different growth stages in an Angus-Brahman multibreed population with a graduated spectrum of genetic variation, raised under variable environmental conditions and diets. We found the gut microbiota structure was changed significantly during growth when preweaning, and fattening calves experienced large variations in diet and environmental changes. However, regardless of the growth stage, we found gut microbiota is significantly influenced by breed composition throughout life. Host genetics explained the relative abundances of 52.2%, 40.0%, and 37.3% of core bacterial taxa at the genus level in preweaning, postweaning, and fattening calves, respectively. Sutterella, Oscillospira, and Roseburia were consistently associated with breed composition at these three growth stages. Especially, butyrate-producing bacteria, Roseburia and Oscillospira, were associated with nine single-nucleotide polymorphisms (SNPs) located in genes involved in the regulation of host immunity and metabolism in the hindgut. Furthermore, minor allele frequency analysis found breed-associated SNPs in the short-chain fatty acids (SCFAs) receptor genes that promote anti-inflammation and enhance intestinal epithelial barrier functions. Our findings provide evidence of dynamic and lifelong host genetic effects upon gut microbiota, regardless of growth stages. We propose that diet, environmental changes, and genetic components may explain observed variation in critical hindgut microbiota throughout life.

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Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

Frontiers in Nutrition ◽

10.3389/fnut.2021.718356 ◽

2021 ◽

Vol 8 ◽

Author(s):

Giovanni Barbara ◽

Maria Raffaella Barbaro ◽

Daniele Fuschi ◽

Marta Palombo ◽

Francesca Falangone ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Cell Damage ◽

Short Chain Fatty Acids ◽

The Body ◽

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Inflammatory Bowel ◽

Irritable Bowel

The intestinal epithelial barrier (IEB) is one of the largest interfaces between the environment and the internal milieu of the body. It is essential to limit the passage of harmful antigens and microorganisms and, on the other side, to assure the absorption of nutrients and water. The maintenance of this delicate equilibrium is tightly regulated as it is essential for human homeostasis. Luminal solutes and ions can pass across the IEB via two main routes: the transcellular pathway or the paracellular pathway. Tight junctions (TJs) are a multi-protein complex responsible for the regulation of paracellular permeability. TJs control the passage of antigens through the IEB and have a key role in maintaining barrier integrity. Several factors, including cytokines, gut microbiota, and dietary components are known to regulate intestinal TJs. Gut microbiota participates in several human functions including the modulation of epithelial cells and immune system through the release of several metabolites, such as short-chain fatty acids (SCFAs). Mediators released by immune cells can induce epithelial cell damage and TJs dysfunction. The subsequent disruption of the IEB allows the passage of antigens into the mucosa leading to further inflammation. Growing evidence indicates that dysbiosis, immune activation, and IEB dysfunction have a role in several diseases, including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gluten-related conditions. Here we summarize the interplay between the IEB and gut microbiota and mucosal immune system and their involvement in IBS, IBD, and gluten-related disorders.

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Honeybee genetics shape the strain-level structure of gut microbiota in social transmission

10.1101/2020.12.17.423353 ◽

2020 ◽

Author(s):

Jiaqiang Wu ◽

Haoyu Lang ◽

Xiaohuan Mu ◽

Zijing Zhang ◽

Qinzhi Su ◽

...

Keyword(s):

Gut Microbiota ◽

Receptor Gene ◽

Level Structure ◽

Social Transmission ◽

Strain Level ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Host Genetics ◽

A Genome ◽

Microbiota Structure

AbstractHoneybee gut microbiota transmitted via social interactions are beneficial to the host health. Although the microbial community is relatively stable, individual variations and high strain-level diversity have been detected across honeybees. Although the bee gut microbiota structure is influenced by environmental factors, the heritability of the gut members and the contribution of the host genetics remains elusive. Considering bees within a colony are not readily genetically identical due to the polyandry of queen, we hypothesize that the microbiota structure can be shaped by host genetics. We used shotgun metagenomics to simultaneously profile the microbiota and host genotypes of individuals from hives of four different subspecies. Gut composition is more distant between genetically different bees at both phylotype- and “sequence-discrete population”-level. We then performed a successive passaging experiment within colonies of hybrid bees generated by artificial insemination, which revealed that the microbial composition dramatically shifts across batches of bees during the social transmission. Specifically, different strains from the phylotype of Snodgrassella alvi are preferentially selected by genetically varied hosts, and strains from different hosts show a remarkably biased distribution of single-nucleotide polymorphism in the Type IV pili loci. A genome-wide association analysis identified that the relative abundance of a cluster of Bifidobacterium strains is associated with the host glutamate receptor gene that is specifically expressed in the bee brain. Finally, mono-colonization of Bifidobacterium with a specific polysaccharide utilization locus impacts the expression and alternative splicing of the gluR-B gene, which is associated with an altered circulating metabolomic profile. Our results indicated that host genetics influence the bee gut composition, and suggest a gut-brain connection implicated in the gut bacterial strain preference. Honeybees have been used extensively as a model organism for social behaviors, genetics, and gut microbiome. Further identification of host genetic function as shaping force of microbial structure will advance our understanding of the host-microbe interactions.

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Gut Microbial Influences on the Mammalian Intestinal Stem Cell Niche

Stem Cells International ◽

10.1155/2017/5604727 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 19

Author(s):

Bailey C. E. Peck ◽

Michael T. Shanahan ◽

Ajeet P. Singh ◽

Praveen Sethupathy

Keyword(s):

Stem Cell ◽

Gut Microbiota ◽

Energy Homeostasis ◽

Environmental Changes ◽

Intestinal Epithelial ◽

Microbe Interactions ◽

Host Microbe Interactions ◽

Cell Niche ◽

Systemic Health ◽

Endocrine Signaling

The mammalian intestinal epithelial stem cell (IESC) niche is comprised of diverse epithelial, immune, and stromal cells, which together respond to environmental changes within the lumen and exert coordinated regulation of IESC behavior. There is growing appreciation for the role of the gut microbiota in modulating intestinal proliferation and differentiation, as well as other aspects of intestinal physiology. In this review, we evaluate the diverse roles of known niche cells in responding to gut microbiota and supporting IESCs. Furthermore, we discuss the potential mechanisms by which microbiota may exert their influence on niche cells and possibly on IESCs directly. Finally, we present an overview of the benefits and limitations of available tools to study niche-microbe interactions and provide our recommendations regarding their use and standardization. The study of host-microbe interactions in the gut is a rapidly growing field, and the IESC niche is at the forefront of host-microbe activity to control nutrient absorption, endocrine signaling, energy homeostasis, immune response, and systemic health.

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Host genetic effects upon the early gut microbiota in a bovine model with graduated spectrum of genetic variation

The ISME Journal ◽

10.1038/s41396-019-0529-2 ◽

2019 ◽

Vol 14 (1) ◽

pp. 302-317 ◽

Cited By ~ 7

Author(s):

Peixin Fan ◽

Beilei Bian ◽

Lin Teng ◽

Corwin D. Nelson ◽

J. Driver ◽

...

Keyword(s):

Genetic Variation ◽

Gut Microbiota ◽

Bos Taurus ◽

Bos Indicus ◽

Nucleotide Polymorphisms ◽

Paternal Genome ◽

Host Genetics ◽

Microbe Interactions ◽

Host Genetic

Abstract Multiple synergistic factors affect the development and composition of mammalian gut microbiota, but effects of host genetics remain unclear. To illuminate the role of host genetics on gut microbiota, we employed animals with a graduated spectrum of genetic variation with minimal environmental influences. We bred 228 calves with linearly varying breed composition from 100% Angus (Bos taurus) to 100% Brahman (Bos indicus), as a proxy for genetic variation, and then raised the offspring in the same environment with identical diets. We hypothesized each breed would harbor distinct gut microbiota due to genetic influence. We found that the gut microbiota of preweaning calves at 3 months old is significantly affected by host genetics, profoundly by paternal genome. We also demonstrate that single nucleotide polymorphisms in host mucin-encoding genes, critical for gut mucosal health, are significantly correlated with both breed composition and mucin-degrading gut bacteria. We further demonstrate host genetics indirectly changes gut microbiota composition via microbe–microbe interactions. These findings indicate a strong contribution by host genetics in shaping the gut microbiota during early life stages, shedding light on impact of animal breeding on gut microbiota, which is associated with animal growth and health.

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Environmental factors dominate over host genetics in shaping human gut microbiota composition

10.1101/150540 ◽

2017 ◽

Cited By ~ 10

Author(s):

Daphna Rothschild ◽

Omer Weissbrod ◽

Elad Barkan ◽

Tal Korem ◽

David Zeevi ◽

...

Keyword(s):

Environmental Factors ◽

Human Genetics ◽

Human Microbiome ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Nucleotide Polymorphisms ◽

Human Gut ◽

Extrinsic Factors ◽

Host Genetics ◽

Microbiome Composition

AbstractHuman gut microbiome composition is shaped by multiple host intrinsic and extrinsic factors, but the relative contribution of host genetic compared to environmental factors remains elusive. Here, we genotyped a cohort of 696 healthy individuals from several distinct ancestral origins and a relatively common environment, and demonstrate that there is no statistically significant association between microbiome composition and ethnicity, single nucleotide polymorphisms (SNPs), or overall genetic similarity, and that only 5 of 211 (2.4%) previously reported microbiome-SNP associations replicate in our cohort. In contrast, we find similarities in the microbiome composition of genetically unrelated individuals who share a household. We define the termbiome-explainabilityas the variance of a host phenotype explained by the microbiome after accounting for the contribution of human genetics. Consistent with our finding that microbiome and host genetics are largely independent, we find significant biome-explainability levels of 16-33% for body mass index (BMI), fasting glucose, high-density lipoprotein (HDL) cholesterol, waist circumference, waist-hip ratio (WHR), and lactose consumption. We further show that several human phenotypes can be predicted substantially more accurately when adding microbiome data to host genetics data, and that the contribution of both data sources to prediction accuracy is largely additive. Overall, our results suggest that human microbiome composition is dominated by environmental factors rather than by host genetics.

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Honeybee Genetics Shape the Strain-Level Structure of Gut Microbiota in Social Transmission

10.21203/rs.3.rs-129095/v1 ◽

2020 ◽

Author(s):

Jiaqiang Wu ◽

Haoyu Lang ◽

Xiaohuan Mu ◽

Zijing Zhang ◽

Qinzhi Su ◽

...

Keyword(s):

Gut Microbiota ◽

Receptor Gene ◽

Level Structure ◽

Social Transmission ◽

Strain Level ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Host Genetics ◽

A Genome ◽

Microbiota Structure

Abstract Background : Honeybee gut microbiota transmitted via social interactions are beneficial to the host health. Although the microbial community is relatively stable, individual variations and high strain-level diversity have been detected across honeybees. Although the bee gut microbiota structure is influenced by environmental factors, the heritability of the gut members and the contribution of the host genetics remains elusive. Considering bees within a colony are not readily genetically identical due to the polyandry of queen, we hypothesize that the microbiota structure can be shaped by host genetics. Results : We used shotgun metagenomics to simultaneously profile the microbiota and host genotypes of individuals from hives of four different subspecies. Gut composition is more distant between genetically different bees at both phylotype- and “sequence-discrete population”-level. We then performed a successive passaging experiment within colonies of hybrid bees generated by artificial insemination, which revealed that the microbial composition dramatically shifts across batches of bees during the social transmission. Specifically, different strains from the phylotype of Snodgrassella alvi are preferentially selected by genetically varied hosts, and strains from different hosts show a remarkably biased distribution of single-nucleotide polymorphism in the Type IV pili loci. A genome-wide association analysis identified that the relative abundance of a cluster of Bifidobacterium strains is associated with the host glutamate receptor gene that is specifically expressed in the bee brain. Finally, mono-colonization of Bifidobacterium with a specific polysaccharide utilization locus impacts the expression and alternative splicing of the gluR-B gene, which is associated with an altered circulating metabolomic profile. Conclusions : Our results indicated that host genetics influence the bee gut composition, and suggest a gut-brain connection implicated in the gut bacterial strain preference. Honeybees have been used extensively as a model organism for social behaviors, genetics, and gut microbiome. Further identification of host genetic function as shaping force of microbial structure will advance our understanding of the host-microbe interactions.

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Honey bee genetics shape the strain-level structure of gut microbiota in social transmission

Microbiome ◽

10.1186/s40168-021-01174-y ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Jiaqiang Wu ◽

Haoyu Lang ◽

Xiaohuan Mu ◽

Zijing Zhang ◽

Qinzhi Su ◽

...

Keyword(s):

Gut Microbiota ◽

Honey Bee ◽

Honey Bees ◽

Level Structure ◽

Social Transmission ◽

Strain Level ◽

Microbial Composition ◽

Shotgun Metagenomics ◽

Host Genetics ◽

Microbiota Structure

Abstract Background Honey bee gut microbiota transmitted via social interactions are beneficial to the host health. Although the microbial community is relatively stable, individual variations and high strain-level diversity have been detected across honey bees. Although the bee gut microbiota structure is influenced by environmental factors, the heritability of the gut members and the contribution of the host genetics remains elusive. Considering bees within a colony are not readily genetically identical due to the polyandry of the queen, we hypothesize that the microbiota structure can be shaped by host genetics. Results We used shotgun metagenomics to simultaneously profile the microbiota and host genotypes of bees from hives of four different subspecies. Gut composition is more distant between genetically different bees at both phylotype- and “sequence-discrete population” levels. We then performed a successive passaging experiment within colonies of hybrid bees generated by artificial insemination, which revealed that the microbial composition dramatically shifts across batches of bees during the social transmission. Specifically, different strains from the phylotype of Snodgrassella alvi are preferentially selected by genetically varied hosts, and strains from different hosts show a remarkably biased distribution of single-nucleotide polymorphism in the Type IV pili loci. Genome-wide association analysis identified that the relative abundance of a cluster of Bifidobacterium strains is associated with the host glutamate receptor gene specifically expressed in the bee brain. Finally, mono-colonization of Bifidobacterium with a specific polysaccharide utilization locus impacts the alternative splicing of the gluR-B gene, which is associated with an increased GABA level in the brain. Conclusions Our results indicated that host genetics influence the bee gut composition and suggest a gut-brain connection implicated in the gut bacterial strain preference. Honey bees have been used extensively as a model organism for social behaviors, genetics, and the gut microbiome. Further identification of host genetic function as a shaping force of microbial structure will advance our understanding of the host-microbe interactions.

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Ameliorative Effects of Peptides Derived from Oyster (Crassostrea gigas) on Immunomodulatory Function and Gut Microbiota Structure in Cyclophosphamide-Treated Mice

Marine Drugs ◽

10.3390/md19080456 ◽

2021 ◽

Vol 19 (8) ◽

pp. 456

Author(s):

Xing-Wei Xiang ◽

Hui-Zhen Zheng ◽

Rui Wang ◽

Hui Chen ◽

Jin-Xing Xiao ◽

...

Keyword(s):

Gut Microbiota ◽

Immune Regulation ◽

Intestinal Flora ◽

Short Chain Fatty Acids ◽

Intestinal Damage ◽

Mrna Levels ◽

Protective Effects ◽

Mucin 2 ◽

Ifn Γ ◽

Microbiota Structure

The intestinal flora is recognized as a significant contributor to the immune system. In this research, the protective effects of oyster peptides on immune regulation and intestinal microbiota were investigated in mice treated with cyclophosphamide. The results showed that oyster peptides restored the indexes of thymus, spleen and liver, stimulated cytokines secretion and promoted the relative mRNA levels of Th1/Th2 cytokines (IL-2, IFN-γ, IL-4 and IL-10). The mRNA levels of Occludin, Claudin-1, ZO-1, and Mucin-2 were up-regulated, and the NF-κB signaling pathway was also activated after oyster peptides administration. Furthermore, oyster peptides treatment reduced the proportion of Firmicutes/Bacteroidetes, increased the relative abundance of Alistipes, Lactobacillus, Rikenell and the content of short-chain fatty acids, and reversed the composition of intestinal microflora similar to that of normal mice. In conclusion, oyster peptides effectively ameliorated cyclophosphamide-induced intestinal damage and modified gut microbiota structure in mice, and might be utilized as a beneficial ingredient in functional foods for immune regulation.

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