Remodeling of the maternal gut microbiome during pregnancy is shaped by parity

Abstract Background The maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies—referred to as maternal parity—as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans. Results Using synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring “quadrads”—each consisting of one mother sow and three piglets—linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth. Conclusions Collectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants.

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Remodeling of the maternal gut microbiome during pregnancy is shaped by parity

10.1101/2020.12.04.412205 ◽

2020 ◽

Author(s):

Alexander SF Berry ◽

Meghann K Pierdon ◽

Ana M. Misic ◽

Megan C. Sullivan ◽

Kevin O’Brien ◽

...

Keyword(s):

Preterm Birth ◽

Gut Microbiome ◽

Infant Health ◽

Lactobacillus Reuteri ◽

Bacterial Species ◽

Human Microbiome ◽

Swine Model ◽

Campylobacter Coli ◽

Maternal Parity ◽

The Impact

AbstractBackgroundThe maternal microbiome has emerged as an important factor in gestational health and outcome and is associated with risk of preterm birth and offspring morbidity. Epidemiological evidence also points to successive pregnancies – referred to as maternal parity – as a risk factor for preterm birth, infant mortality, and impaired neonatal growth. Despite the fact that both the maternal microbiome and parity are linked to maternal-infant health, the impact of parity on the microbiome remains largely unexplored, in part due to the challenges of studying parity in humans.ResultsUsing synchronized pregnancies and dense longitudinal monitoring of the microbiome in pigs, we describe a microbiome trajectory during pregnancy and determine the extent to which parity modulates this trajectory. We show that the microbiome changes reproducibly during gestation and that this remodeling occurs more rapidly as parity increases. At the time of parturition, parity was linked to the relative abundance of several bacterial species, including Treponema bryantii, Lactobacillus amylovorus, and Lactobacillus reuteri. Strain tracking carried out in 18 maternal-offspring ‘quadrads’ – each consisting of one mother sow and three piglets – linked maternal parity to altered levels of Akkermansia muciniphila, Prevotella stercorea, and Campylobacter coli in the infant gut 10 days after birth.ConclusionsCollectively, these results identify parity as an important environmental factor that modulates the gut microbiome during pregnancy and highlight the utility of a swine model for investigating the microbiome in maternal-infant health. In addition, our data show that the impact of parity extends beyond the mother and is associated with alterations in the community of bacteria that colonize the offspring gut early in life. The bacterial species we identified as parity-associated in the mother and offspring have been shown to influence host metabolism in other systems, raising the possibility that such changes may influence host nutrient acquisition or utilization. These findings, taken together with our observation that even subtle differences in parity are associated with microbiome changes, underscore the importance of considering parity in the design and analysis of human microbiome studies during pregnancy and in infants.

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Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome

mBio ◽

10.1128/mbio.01343-17 ◽

2017 ◽

Vol 8 (5) ◽

Cited By ~ 89

Author(s):

Tanja V. Maier ◽

Marianna Lucio ◽

Lang Ho Lee ◽

Nathan C. VerBerkmoes ◽

Colin J. Brislawn ◽

...

Keyword(s):

Lipid Metabolism ◽

Gut Microbiome ◽

Resistant Starch ◽

Metabolic Pathways ◽

Bacterial Species ◽

Human Microbiome ◽

Rrna Gene ◽

Gut Microbes ◽

Mechanistic Understanding ◽

The Impact

ABSTRACT Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS. We determined the impact of RS on the gut microbiome and metabolic pathways in the gut, using a combination of “omics” approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics. This multiomics approach captured changes in the abundance of specific bacterial species, proteins, and metabolites after a diet high in resistant starch (HRS), providing key insights into the influence of dietary interventions on the gut microbiome. The combined data showed that a high-RS diet caused an increase in the ratio of Firmicutes to Bacteroidetes , including increases in relative abundances of some specific members of the Firmicutes and concurrent increases in enzymatic pathways and metabolites involved in lipid metabolism in the gut. IMPORTANCE This work was undertaken to obtain a mechanistic understanding of the complex interplay between diet and the microorganisms residing in the intestine. Although it is known that gut microbes play a key role in digestion of the food that we consume, the specific contributions of different microorganisms are not well understood. In addition, the metabolic pathways and resultant products of metabolism during digestion are highly complex. To address these knowledge gaps, we used a combination of molecular approaches to determine the identities of the microorganisms in the gut during digestion of dietary starch as well as the metabolic pathways that they carry out. Together, these data provide a more complete picture of the function of the gut microbiome in digestion, including links between an RS diet and lipid metabolism and novel linkages between specific gut microbes and their metabolites and proteins produced in the gut.

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A Tree of Human Gut Bacterial Species and its Applications to Metagenomics and Metaproteomics Data Analysis

10.1101/2020.09.24.311720 ◽

2020 ◽

Author(s):

Moses Stamboulian ◽

Thomas G. Doak ◽

Yuzhen Ye

Keyword(s):

Gut Microbiome ◽

Phylogenetic Trees ◽

Bacterial Species ◽

Taxonomic Composition ◽

Marker Genes ◽

Missing Information ◽

Human Gut ◽

Taxonomic Profiling ◽

Tree Building ◽

The Impact

Abstract1BackgroundRecent advances in genome and metagenome sequencing have dramatically enriched the collection of genomes of bacterial species related to human health and diseases. In metagenomic studies phylogenetic trees are commonly used to depict, describe, and compare the bacterial members of the community under study. The most accurate tree-building algorithms now use large sets of marker genes taken from across genomes. However, many of the current bacterial genomes were assembled from metagenomic datasets (i.e., metagenome assembled genomes, MAGs), and often contain missing information. It is therefore important to study how well the phylogeny approach performs on such genomes. Further, phylogeny methods are not perfect and it is important to know how reliable an inferred tree is.ResultsHere we examined the impact of incompleteness of the genomes on the tree reconstruction, and we showed that phylogeny approaches including RAxML (which handles missing data explicitly) and FastTree generally performed well on simulated collection of 400 genomes with missing information. As RAxML is computationally prohibitive for the much larger collections of gut genomes, we chose FastTree to build a unified tree of human-gut associated bacterial species (referred to as gut tree), including more than 3000 genomes, most of which are incomplete. We developed two downstream applications of the gut tree: peptide-centric analysis of metaproteomics datasets; and taxonomic characterization of metagenomic sequences. In both applications, the gut tree provided the basis for quantification of species composition at various taxonomic resolutions.ConclusionsThe gut tree presented in this study provides a useful framework for taxonomic profiling of human gut microbiome. Including MAGs in the tree provides more comprehensive representation of microbial species diversity associated with human gut, important for studying the taxonomic composition of gut microbiome.Availability and ImplementationThe tree construction pipeline and downstream applications of the gut tree are freely available at https://github.com/mgtools/guttree.

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Pharmacologically induced weight loss is associated with distinct gut microbiome changes in obese rats

10.1101/2021.05.06.442639 ◽

2021 ◽

Author(s):

Silvia Raineri ◽

Julia A Sherriff ◽

Kevin S.J Thompson ◽

Huw Jones ◽

Paul T Pfluger ◽

...

Keyword(s):

Weight Loss ◽

Food Intake ◽

Detailed Analysis ◽

Relative Abundance ◽

Gut Microbiome ◽

Bacterial Species ◽

Shotgun Metagenomics ◽

Fecal Microbiome ◽

Obese Rats ◽

The Impact

Background: Obesity, metabolic disease and some psychiatric conditions are associated with changes to relative abundance of bacterial species and specific genes in the fecal microbiome. Little is known about the impact of pharmacologically induced weight loss on distinct gut microbiome species and their respective gene programs in obese individuals. Results: Using shotgun metagenomics, the composition of the microbiome was obtained for two cohorts of obese female Wistar rats (n=10-12, total of 82) maintained on a high fat diet before and after a 42-day treatment with a panel of four anti-obesity drugs (tacrolimus/FK506, bupropion, naltrexone and sibutramine), alone or in combination. We found that sibutramine treatment induced consistent weight loss through reducing food intake. Decreased weight loss in sibutramine-treated rats was associated with changes to the gut microbiome that included increased beta-diversity, increased Bacteroides/Firmicutes ratio and increased relative abundance of multiple Bacteroides species. In addition, the relative abundance of multiple genes was found to be differentially abundant, including significant reductions in components of flagellum and genes involved in flagellum assembly. Conclusions: This study provides a large resource comprising complete shotgun metagenomics datasets of the fecal microbiome coupled with weight change and food intake at day 3, day 15 and day 42 from 82 obese rats treated with a range of compounds used for weight loss, which are available to the community for detailed analysis. Furthermore, by conducting a detailed analysis of the microbiome associated with sibutramine-induced weight loss, we have identified multiple weight-loss associated microbial taxa and pathways. These include a reduction in components of flagellum and the flagellum assembly pathway that points to a potential role of sibutramine-induced weight-loss on regulating bacterially driven anti-inflammatory responses.

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Changes in the Gut Microbiome Community of nonhuman primate following radiation injury

10.21203/rs.3.rs-38247/v1 ◽

2020 ◽

Author(s):

Raj Kalkeri ◽

Kevin Walters ◽

William Van Der Pol ◽

Braden C. McFarland ◽

Nathan Fisher ◽

...

Keyword(s):

Radiation Exposure ◽

Gut Microbiome ◽

Radiation Injury ◽

Lactobacillus Reuteri ◽

Whole Body ◽

High Dose ◽

Microbiome Composition ◽

Post Irradiation ◽

High Doses ◽

The Impact

Abstract Background Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Methods Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) one day prior and one and four days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD70 − 80/60). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform. Results Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Conclusion Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury.

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Systematic Review: The Impact of Cancer Treatment on the Gut and Vaginal Microbiome in Women With a Gynecological Malignancy

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000999 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1550-1559 ◽

Cited By ~ 9

Author(s):

Ann Muls ◽

Jervoise Andreyev ◽

Susan Lalondrelle ◽

Alexandra Taylor ◽

Christine Norton ◽

...

Keyword(s):

Systematic Review ◽

Cancer Treatment ◽

Systematic Reviews ◽

Gut Microbiome ◽

Bacterial Species ◽

Gastrointestinal Toxicity ◽

Vaginal Microbiome ◽

Cancer Treatments ◽

Gynecological Malignancy ◽

The Impact

Background and AimWorldwide, 1,470,900 women are diagnosed yearly with a gynecological malignancy (21,000 in the UK). Some patients treated with pelvic radiotherapy develop chronic changes in their bowel function. This systematic review summarizes current research on the impact of cancer treatment on the gut and vaginal microbiome in women with a gynecological malignancy.MethodsThe Preferred reporting Items for Systematic Reviews and Meta-analyses guidelines for systematic reviews were used to ensure transparent and complete reporting. Quantitative studies exploring the gut or vaginal microbiome in this patient cohort were included. Animal studies were excluded. There were no language restrictions.ResultsNo studies examined the possible effects of surgery or chemotherapy for gynecological cancers on the gut or vaginal microbiome.Three prospective cohort studies were identified using sequencing of changes in the gut microbiome reporting on a total of 23 women treated for gynecological cancer. All studies included patients treated with radiotherapy with a dosage ranging from 43.0 to 54.0 Gy. Two studies assessed gastrointestinal toxicity formally; 8 women (57%) developed grade 2 or 3 diarrhea during radiotherapy. The outcomes suggest a correlation between changes in the intestinal microbiome and receiving radiotherapy and showed a decrease in abundance and diversity of the intestinal bacterial species. Before radiotherapy, those who developed diarrhea had an increased abundance of Bacteroides, Dialister, and Veillonella (P < 0.01), and a decreased abundance of Clostridium XI and XVIII, Faecalibacterium, Oscillibacter, Parabacteroides, Prevotella, and unclassified bacteria (P < 0.05).ConclusionThe limited evidence to date implies that larger studies including both the vaginal and gut microbiome in women treated for a gynecological malignancy are warranted to explore the impact of cancer treatments on the microbiome and its relation to developing long-term gastrointestinal toxicity. This may lead to new avenues to stratify those at risk and explore personalized treatment options and prevention of gastrointestinal consequences of cancer treatments.

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Dynamic gut microbiome changes to low-iron challenge

Applied and Environmental Microbiology ◽

10.1128/aem.02307-20 ◽

2020 ◽

Author(s):

Genevieve L. Coe ◽

Nicholas V. Pinkham ◽

Arianna I. Celis ◽

Christina Johnson ◽

Jennifer L. DuBois ◽

...

Keyword(s):

Mouse Model ◽

Gut Microbiome ◽

Iron Homeostasis ◽

Human Microbiome ◽

Taxonomic Structure ◽

Dietary Iron ◽

Iron Cycling ◽

Highly Sensitive ◽

And Function ◽

The Impact

Iron is an essential micronutrient for life. In mammals, dietary iron is primarily absorbed in the small intestine. Currently, the impacts of dietary iron on the taxonomic structure and function of the gut microbiome and reciprocal effects on the animal host are not well understood. Here, we establish a mouse model of low-iron challenge in which intestinal biomarkers and reduced fecal iron reveal iron stress while serum iron and mouse behavioral markers indicate maintenance of iron homeostasis. We show that the diversity of the gut microbiome in conventional C57BL/6 mice changes dramatically during two-weeks on a low-iron diet. We also show the effects of a low-iron diet on microbiome diversity are long-lasting and not easily recovered when iron is returned to the diet. Finally, after optimizing taxon association methods, we show that some bacteria are unable to fully recover after the low-iron challenge and appear to be extirpated from the gut entirely. In particular, OTUs from the Prevotellaceae and Porphyromonadaceae families and Bacteroidales order are highly sensitive to low-iron conditions, while other seemingly insensitive OTUs recover. These results provide new insights into the iron requirements of gut microbiome members and add to the growing understanding of mammalian iron cycling. IMPORTANCE All cells need iron. Both too much iron and too little lead to diseases and unwanted outcomes. Although the impact of dietary iron on human cells and tissues has been well studied, there is currently a lack of understanding about how different levels of iron influence the abundant and diverse members of the human microbiome. This study develops a well-characterized mouse model for studying low-iron levels and identifies key groups of bacteria that are most affected. We found that the microbiome undergoes large changes when iron is removed from the diet but that many individual bacteria are able to rebound when iron levels are changed by to normal. That said, a select few members, referred to as “iron-sensitive” bacteria seem to be lost. This study begins to identify individual members of the mammalian microbiome most affected by changes in dietary iron levels.

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Changes in the Gut Microbiome Community of nonhuman primate following radiation injury

10.21203/rs.3.rs-42665/v2 ◽

2020 ◽

Author(s):

Raj Kalkeri ◽

Kevin Walters ◽

William Van Der Pol ◽

Braden C. McFarland ◽

Nathan Fisher ◽

...

Keyword(s):

Radiation Exposure ◽

Gut Microbiome ◽

Radiation Injury ◽

Lactobacillus Reuteri ◽

Whole Body ◽

High Dose ◽

Microbiome Composition ◽

Post Irradiation ◽

High Doses ◽

The Impact

Abstract Background: Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) one day prior and one and four days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD70-80/60). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform. Results: Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day +4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Conclusions: Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury.

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Distinct impact of antibiotics on the gut microbiome and resistome: a longitudinal multicenter cohort study

BMC Biology ◽

10.1186/s12915-019-0692-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 20

Author(s):

Matthias Willmann ◽

Maria J. G. T. Vehreschild ◽

Lena M. Biehl ◽

Wichard Vogel ◽

Daniela Dörfel ◽

...

Keyword(s):

Gut Microbiome ◽

Human Microbiome ◽

Antibiotic Resistance Genes ◽

Antimicrobial Treatment ◽

Treatment Programs ◽

Defined Daily Dose ◽

Multicenter Cohort Study ◽

Shotgun Metagenomics ◽

Antibiotic Drugs ◽

The Impact

Abstract Background The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there is an urgent need to develop a more quantitative knowledge base that can enable predictions of the impact of individual antibiotics on the human gut microbiome and resistome. Results Using shotgun metagenomics, we quantified changes in the gut microbiome in two cohorts of hematological patients receiving prophylactic antibiotics; one cohort was treated with ciprofloxacin in a hospital in Tübingen and the other with cotrimoxazole in a hospital in Cologne. Analyzing this rich longitudinal dataset, we found that gut microbiome diversity was reduced in both treatment cohorts to a similar extent, while effects on the gut resistome differed. We observed a sharp increase in the relative abundance of sulfonamide antibiotic resistance genes (ARGs) by 148.1% per cumulative defined daily dose of cotrimoxazole in the Cologne cohort, but not in the Tübingen cohort treated with ciprofloxacin. Through multivariate modeling, we found that factors such as individual baseline microbiome, resistome, and plasmid diversity; liver/kidney function; and concurrent medication, especially virostatic agents, influence resistome alterations. Strikingly, we observed different effects on the plasmidome in the two treatment groups. There was a substantial increase in the abundance of ARG-carrying plasmids in the cohort treated with cotrimoxazole, but not in the cohort treated with ciprofloxacin, indicating that cotrimoxazole might contribute more efficiently to the spread of resistance. Conclusions Our study represents a step forward in developing the capability to predict the effect of individual antimicrobials on the human microbiome and resistome. Our results indicate that to achieve this, integration of the individual baseline microbiome, resistome, and mobilome status as well as additional individual patient factors will be required. Such personalized predictions may in the future increase patient safety and reduce the spread of resistance. Trial registration ClinicalTrials.gov, NCT02058888. Registered February 10 2014

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