Developmental Stage, Solid Food Introduction and Suckling Cessation Differentially Influence the Co-maturation of the Gut Microbiota and Intestinal Epithelium in Rabbits

Abstract Background In mammals, the establishment around weaning of a symbiotic relationship between the gut microbiota and its host determines long-term health. Objective The aim of this study was to identify the factors driving the co-maturation of the gut microbiota and intestinal epithelium at the suckling-to-weaning transition. We hypothesized that developmental stage, solid food ingestion and suckling cessation contribute to this process. Methods From birth to day 18, Hyplus rabbits were exclusively suckling. From day 18 to day 25, rabbits were i) exclusively suckling or ii) suckling and ingesting solid food or iii) exclusively ingesting solid food. The microbiota (16S amplicon sequencing), metabolome (nuclear magnetic resonance) and epithelial gene expression (high-throughput qPCR) were analyzed in the caecum at day 18 and 25. Results The microbiota structure and metabolic activity were modified with age when rabbits remained exclusively suckling. The epithelial gene expression of nutrient transporters, proliferation markers and innate immune factors were also regulated with age (e.g., 1.5-fold decrease of TLR5). Solid food ingestion by suckling rabbits had a major effect on the gut microbiota by increasing its α-diversity, remodeling its structure (e.g., 6.3-fold increase of Ruminococcaceae) and metabolic activity (e.g., 4.6-fold increase of butyrate). Solid food introduction also regulated the gene expression of nutrient transporters, differentiation markers and innate immune factors in the epithelium (e.g., 3-fold increase of NOS2). Suckling cessation had no effect on the microbiota while it regulated the expression of genes involved in epithelial differentiation and immunoglobulin transport (e.g., 2.5-increase of PIGR). Conclusion In rabbits, the maturation of the microbiota at the suckling-to-weaning transition is driven by the introduction of solid food and to a lesser extent by developmental stage. In contrast, the maturation of the intestinal epithelium at the suckling-to-weaning transition is under the influence of developmental stage, solid food introduction and suckling cessation.

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Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

10.21203/rs.3.rs-20279/v2 ◽

2020 ◽

Author(s):

Maria Carmen Collado ◽

Marta Selma-Royo ◽

Marta Calatayud ◽

Izaskun García-Mantrana ◽

Anna Parra-Llorca ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Epithelium ◽

Innate Immune System ◽

Host Response ◽

Innate Immune ◽

Epithelial Barrier ◽

Intestinal Function ◽

Intestinal Maturation

Abstract Background: Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods: Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results: Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions: Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.

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Su1998 – Early Life Solid Food Ingestion Remodels the Gut Microbiota Compostion and Increases the Production of Protective Bacterial Metabolites

Gastroenterology ◽

10.1016/s0016-5085(19)38632-9 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-685-S-686

Author(s):

Martin Beaumont ◽

Charlotte Paës ◽

Laurent Cauquil ◽

Patrick Aymard ◽

Céline Barilly ◽

...

Keyword(s):

Gut Microbiota ◽

Early Life ◽

Solid Food ◽

Food Ingestion ◽

Bacterial Metabolites

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Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro

mBio ◽

10.1128/mbio.01453-15 ◽

2015 ◽

Vol 6 (6) ◽

Cited By ~ 33

Author(s):

Alexandra Dostal ◽

Christophe Lacroix ◽

Lea Bircher ◽

Van Thanh Pham ◽

Rainer Follador ◽

...

Keyword(s):

Hydrogen Production ◽

Gut Microbiota ◽

Metabolic Activity ◽

Fold Increase ◽

Fe Deficiency ◽

Batch Cultures ◽

Expression Of Genes ◽

Fermentation Model ◽

Butyrate Production

ABSTRACTThe aim of this study was to investigate the effect of iron (Fe) availability on butyrate production in the complex bacterial ecosystem of the human gut. Hence, different Fe availabilities were mimicked in anin vitrocolonic fermentation model (the polyfermenter intestinal model called PolyFermS) inoculated with immobilized gut microbiota from a child and in batch cultures of the butyrate producerRoseburia intestinalis. Shifts in the microbial community (16S rRNA sequencing and quantitative PCR), metabolic activity (high-performance liquid chromatography), and expression of genes involved in butyrate production were assessed. In the PolyFermS, moderate Fe deficiency resulted in a 1.4-fold increase in butyrate production and a 5-fold increase in butyryl-coenzyme A (CoA):acetate CoA-transferase gene expression, while very strong Fe deficiency significantly decreased butyrate concentrations and butyrate-producing bacteria compared with the results under normal Fe conditions. Batch cultures ofR. intestinalisgrown in a low-Fe environment preferentially produced lactate and had reduced butyrate and hydrogen production, in parallel with upregulation of the lactate dehydrogenase gene and downregulation of the pyruvate:ferredoxin-oxidoreductase gene. In contrast, under high-Fe conditions,R. intestinaliscultures showed enhanced butyrate and hydrogen production, along with increased expression of the corresponding genes, compared with the results under normal-Fe conditions. Our data reveal the strong regulatory effect of Fe on gut microbiota butyrate producers and on the concentrations of butyrate, which contributes to the maintenance of host gut health.IMPORTANCEFe deficiency is one of the most common nutritional deficiencies worldwide and can be corrected by Fe supplementation. In thisin vitrostudy, we show that environmental Fe concentrations in a continuous gut fermentation model closely mimicking a child's gut microbiota strongly affect the composition of the gut microbiome and its metabolic activity, particularly butyrate production. The differential expression of genes involved in the butyrate production pathway under different Fe conditions and the enzyme cofactor role of Fe explain the observed modulation of butyrate production. Our data reveal that the level of dietary Fe reaching the colon affects the microbiome, and its essential function of providing the host with beneficial butyrate.

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Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function

Microbiome ◽

10.1186/s40168-020-00940-8 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

M. Selma-Royo ◽

M. Calatayud Arroyo ◽

I. García-Mantrana ◽

A. Parra-Llorca ◽

R. Escuriet ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Epithelium ◽

Innate Immune System ◽

Host Response ◽

Innate Immune ◽

Epithelial Barrier ◽

Intestinal Function ◽

Intestinal Maturation

Abstract Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. Trial registration NCT03552939.

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Multi-Omics Analysis Reveals Changes in the Intestinal Microbiome, Transcriptome, and Methylome in a Rat Model of Chronic Non-bacterial Prostatitis: Indications for the Existence of the Gut-Prostate Axis

Frontiers in Physiology ◽

10.3389/fphys.2021.753034 ◽

2022 ◽

Vol 12 ◽

Author(s):

Junsheng Liu ◽

Yihe Wang ◽

Guangwen Zhang ◽

Liu Liu ◽

Xichun Peng

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Gut Microbiota ◽

Rat Model ◽

Intestinal Epithelium ◽

Barrier Function ◽

Epigenetic Mechanism ◽

Omics Analysis ◽

Bacterial Prostatitis ◽

Rdna Sequencing

Chronic non-bacterial prostatitis (CNP) is one of the most prevalent diseases in human males worldwide. In 2005, the prostate-gut axis was first proposed to indicate the close relationship between the prostate and the intestine. This study investigated CNP-induced changes of the gut microbiota, gene expression and DNA methylation in a rat model by using multi-omics analysis. Firstly, 16S rDNA sequencing presented an altered structure of the microbiota in cecum of CNP rats. Then, transcriptomic analysis revealed that the expression of 185 genes in intestinal epithelium was significantly changed by CNP. These changes can participate in the immune system, digestive system, metabolic process, etc. Finally, methylC-capture sequencing (MCC-Seq) found 73,232 differentially methylated sites (DMSs) in the DNA of intestinal epithelium between control and CNP rats. A combined analysis of methylomics and transcriptomics suggested an epigenetic mechanism for CNP-induced differential expression genes correlated with intestinal barrier function, immunity, metabolism, enteric infectious disease, etc. More importantly, the transcriptomic, methylomic and gut microbial changes were highly correlated with multiple processes including intestinal immunity, metabolism and epithelial barrier function. In this study, disrupted homeostasis in the gut microbiota, gene expression and DNA methylation were reported in CNP, which supports the existence of the gut-prostate axis.

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Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

10.21203/rs.3.rs-20279/v1 ◽

2020 ◽

Author(s):

Marta Selma-Royo ◽

Marta Calatayud ◽

Izaskun García-Mantrana ◽

Anna Parra-Llorca ◽

Ramón Escuriet ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Epithelium ◽

Innate Immune System ◽

Host Response ◽

Innate Immune ◽

Epithelial Barrier ◽

Intestinal Function ◽

Intestinal Maturation

Abstract Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.

Download Full-text