The Bifidogenic Effect Revisited—Ecology and Health Perspectives of Bifidobacterial Colonization in Early Life

Extensive microbial colonization of the infant gastrointestinal tract starts after parturition. There are several parallel mechanisms by which early life microbiome acquisition may proceed, including early exposure to maternal vaginal and fecal microbiota, transmission of skin associated microbes, and ingestion of microorganisms present in breast milk. The crucial role of vertical transmission from the maternal microbial reservoir during vaginal delivery is supported by the shared microbial strains observed among mothers and their babies and the distinctly different gut microbiome composition of caesarean-section born infants. The healthy infant colon is often dominated by members of the keystone genus Bifidobacterium that have evolved complex genetic pathways to metabolize different glycans present in human milk. In exchange for these host-derived nutrients, bifidobacteria’s saccharolytic activity results in an anaerobic and acidic gut environment that is protective against enteropathogenic infection. Interference with early-life microbiota acquisition and development could result in adverse health outcomes. Compromised microbiota development, often characterized by decreased abundance of Bifidobacterium species has been reported in infants delivered prematurely, delivered by caesarean section, early life antibiotic exposure and in the case of early life allergies. Various microbiome modulation strategies such as probiotic, prebiotics, synbiotics and postbiotics have been developed that are able to generate a bifidogenic shift and help to restore the microbiota development. This review explores the evolutionary ecology of early-life type Bifidobacterium strains and their symbiotic relationship with humans and discusses examples of compromised microbiota development in which stimulating the abundance and activity of Bifidobacterium has demonstrated beneficial associations with health.

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Successional stages in infant gut microbiota maturation

10.1101/2021.06.25.450009 ◽

2021 ◽

Author(s):

Leen Beller ◽

Ward Deboutte ◽

Gwen Falony ◽

Sara Vieira Silva ◽

Raul Tito ◽

...

Keyword(s):

Gut Microbiota ◽

Early Life ◽

Microbial Colonization ◽

Maturation Stage ◽

Gut Flora ◽

Microbiome Composition ◽

Gut Colonization ◽

Maturation Stages ◽

Colonization Process ◽

First Year Of Life

Background: Disturbances in the primary colonization of the infant gut can result in life-long consequences and have been associated with a range of host conditions. Although early life factors have been shown to affect the infant gut microbiota development, our current understanding of the human gut colonization in early life remains limited. To gain more insights in the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (total number of samples, n=303). To evaluate gut microbiota maturation transition towards an adult configuration, we compared the microbiome composition of the infants to the Flemish Gut Flora Project population (n=1,106). Results: We observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, genus predominance was observed to shift from Escherichia over Bifidobacterium to Bacteroides. Both disease and antibiotic treatment were observed to be associated occasionally with gut microbiota maturation stage regression, a transient setback in microbiota maturation dynamics. Although the studied microbiota trajectories evolved to more adult-like constellations, microbiome community typing against the background of the Flemish Gut Flora Project (FGFP) cohort clustered all infant samples within the (in adults) potentially dysbiotic Bact2 enterotype. Conclusion: We confirmed similarities between infant gut microbial colonization and adult dysbiosis. A profound knowledge about the primary gut colonization process in infants might provide crucial insights into how the secondary colonization of a dysbiotic adult gut can be redirected.

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Maternal effects on early-life gut microbiome maturation in a wild nonhuman primate

10.1101/2021.11.06.467515 ◽

2021 ◽

Author(s):

Alice Baniel ◽

Lauren Petrullo ◽

Arianne Mercer ◽

Laurie Reitsema ◽

Sierra Sams ◽

...

Keyword(s):

Maternal Effects ◽

Gut Microbiome ◽

Early Life ◽

Amplicon Sequencing ◽

Microbial Colonization ◽

Fecal Samples ◽

Microbiome Composition ◽

16S Rrna Amplicon Sequencing ◽

Gut Colonization ◽

First Time

Early-life gut microbial colonization is an important process shaping host physiology, immunity and long-term health outcomes in humans and other animals. However, our understanding of this dynamic process remains poorly investigated in wild animals, where developmental mechanisms can be better understood within ecological and evolutionary relevant contexts. Using 16s rRNA amplicon sequencing on 525 fecal samples from a large cohort of infant and juvenile geladas (Theropithecus gelada), we characterized gut microbiome maturation during the first three years of life and assessed the role of maternal effects in shaping offspring microbiome assembly. Microbial diversity increased rapidly in the first months of life, followed by more gradual changes until weaning. As expected, changes in gut microbiome composition and function with increasing age reflected progressive dietary transitions: in early infancy when infants rely heavily on their mother's milk, microbes that facilitate milk glycans and lactose utilization dominated, while later in development as graminoids are progressively introduced into the diet, microbes that metabolize plant complex polysaccharides became dominant. Furthermore, the microbial community of nursing infants born to first-time (primiparous) mothers was more "milk-oriented" compared to similarly-aged infants born to experienced (multiparous) mothers. Comparisons of matched mother-offspring fecal samples to random dyads did not support vertical transmission as a conduit for these maternal effects, which instead could be explained by slower phenotypic development (and associated slower gut microbiome maturation) in infants born to first-time mothers. Together, our findings highlight the dynamic nature of gut colonization

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Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets

International Journal of Molecular Sciences ◽

10.3390/ijms21020503 ◽

2020 ◽

Vol 21 (2) ◽

pp. 503 ◽

Cited By ~ 4

Author(s):

Quanhang Xiang ◽

Xiaoyu Wu ◽

Ye Pan ◽

Liu Wang ◽

Chenbin Cui ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Relative Abundance ◽

Early Life ◽

System Development ◽

Fecal Microbiota ◽

Microbial Colonization ◽

Life Period ◽

Weaning Stress ◽

Immune System Development

Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a “window of opportunity” for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.

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2843. Maternal Fecal Transplantation to Infants Born by Cesarean Section: Safety and Feasibility

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz359.148 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S68-S68

Author(s):

Otto Helve ◽

Katri Korpela ◽

Kaija-Leena Kolho ◽

Terhi Saisto ◽

Kirsi Skogberg ◽

...

Keyword(s):

Cesarean Section ◽

Early Life ◽

Fecal Microbiota ◽

Microbial Colonization ◽

Intestinal Microbiome ◽

Fecal Samples ◽

Fecal Transplantation ◽

Fecal Microbiome ◽

Cesarean Section Delivery ◽

First Feeding

Abstract Background A complication of cesarean section delivery is its interference with the normal intestinal colonization of the infant, affecting the development of immune system in early life—a process that has been associated with long-term morbidity, such as allergy and diabetes. We evaluated, in CS-delivered infants, whether the normal intestinal microbiome and its early life development could be restored by immediate postnatal transfer of maternal fecal microbiota to the newborn. Methods Seventeen healthy mothers with planned elective CS were recruited and screened thoroughly for infections, after which 7 mothers were included in the study. A fecal sample was processed according to a transplantation protocol and an aliquot (3–7 mg) was orally administered in breast-milk to the newborn during the first feeding. The infants were followed and fecal samples were gathered during the first 12 weeks of age and subsequently at the age of 8–18 months. Results The bacterial communities in the fecal samples of the mothers and their offspring were analyzed by sequencing of 16S rRNA amplicons from isolated fecal DNA and compared with that of 11 nontreated CS-delivered infants and 34 vaginally delivered infants. The fecal microbiota at 3 and 12 weeks was similar between treated CS and vaginally delivered infants, in contrast to that of the untreated CS-delivered infants both in overall composition (P = 0.001, Figure) and development of early-life signature bacteria, i.e., bacteroides and bifidobacteria and clostridia (P < 0.0001). Conclusion The seeding of maternal fecal microbes to the newborn intestine can be safely and successfully mimicked in elective CS by transferring a small amount of maternal fecal microbiome orally to the newborn infant. In these infants, this process results in a microbial development that is highly similar to that of the vaginally born infants, and provides support for the hypothesis that microbial colonization in early life results from a maternal fecal transfer. Disclosures All Authors: No reported Disclosures.

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Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients

Journal of Medical Case Reports ◽

10.1186/s13256-020-02583-7 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Fengqiong Liu ◽

Shanliang Ye ◽

Xin Zhu ◽

Xuesong He ◽

Shengzhou Wang ◽

...

Keyword(s):

B Cells ◽

Fecal Microbiota Transplantation ◽

Gastrointestinal Symptoms ◽

Fecal Microbiota ◽

Case Presentation ◽

Microbiome Composition ◽

Operational Taxonomic Units ◽

Gut Dysbiosis ◽

Rehabilitative Intervention ◽

Oral Capsule

Abstract Background To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Case presentation A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT. Conclusions After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

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Dysbiosis of intestinal microbiota in early life aggravates high-fat diet induced dysmetabolism in adult mice

BMC Microbiology ◽

10.1186/s12866-021-02263-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Z. H. Miao ◽

W. X. Zhou ◽

R. Y. Cheng ◽

H. J. Liang ◽

F. L. Jiang ◽

...

Keyword(s):

Intestinal Microbiota ◽

High Fat Diet ◽

Early Life ◽

Fasting Blood Glucose ◽

Fecal Microbiota ◽

Long Term Effects ◽

High Fat ◽

Host Animal ◽

Intestinal Microbes ◽

Lipid Metabolism Disorders

Abstract Background Accumulating evidence have shown that the intestinal microbiota plays an important role in prevention of host obesity and metabolism disorders. Recent studies also demonstrate that early life is the key time for the colonization of intestinal microbes in host. However, there are few studies focusing on possible association between intestinal microbiota in the early life and metabolism in adulthood. Therefore the present study was conducted to examine whether the short term antibiotic and/or probiotic exposure in early life could affect intestinal microbes and their possible long term effects on host metabolism. Results A high-fat diet resulted in glucose and lipid metabolism disorders with higher levels of visceral fat rate, insulin-resistance indices, and leptin. Exposure to ceftriaxone in early life aggravated the negative influences of a high-fat diet on mouse physiology. Orally fed TMC3115 protected mice, especially those who had received treatment throughout the whole study, from damage due to a high-fat diet, such as increases in levels of fasting blood glucose and serum levels of insulin, leptin, and IR indices. Exposure to ceftriaxone during the first 2 weeks of life was linked to dysbiosis of the fecal microbiota with a significant decrease in the species richness and diversity. However, the influence of orally fed ceftriaxone on the fecal microbiota was limited to 12 weeks after the termination of treatment. Of note, at week 12 there were still some differences in the composition of intestinal microbiota between mice provided with high fat diet and antibiotic exposure and those only fed a high fat diet. Conclusions These results indicated that exposure to antibiotics, such as ceftriaxone, in early life may aggravate the negative influences of a high-fat diet on the physiology of the host animal. These results also suggest that the crosstalk between the host and their intestinal microbiota in early life may be more important than that in adulthood, even though the same intestinal microbes are present in adulthood.

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Alterations of fecal microbiome characteristics by dietary soy isoflavone ingestion in growing pigs infected with porcine reproductive and respiratory syndrome virus

Journal of Animal Science ◽

10.1093/jas/skaa156 ◽

2020 ◽

Vol 98 (6) ◽

Author(s):

Brooke N Smith ◽

Stephen A Fleming ◽

Mei Wang ◽

Ryan N Dilger

Keyword(s):

Control Diet ◽

Fecal Microbiota ◽

Growing Pigs ◽

Respiratory Syndrome Virus ◽

Post Inoculation ◽

Unifrac Distance ◽

Infectious Dose ◽

Fecal Microbiome ◽

Microbiome Composition ◽

Experimental Treatments

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important disease, and the ingestion of soy isoflavones (ISF) may benefit PRRSV-infected pigs due to demonstrated anti-inflammatory and antiviral properties. The objective of this study was to quantify the effects of ISF consumption on fecal microbiome characteristics at different timepoints across a disease challenge and determine whether any changes, if present, elude to potential biological mechanisms for previously observed performance benefits. In total, 96 weaned barrows were group-housed in a Biosafety Level-2 containment facility and allotted to one of three experimental treatments that were maintained throughout the study: noninfected pigs receiving an ISF-devoid control diet (NEG, n = 24) and infected pigs receiving either the control diet (POS, n = 36) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n = 36). Following a 7-d adaptation, pigs were inoculated intranasally with either a sham-control (phosphate-buffered saline) or live PRRSV (1 × 105 median tissue culture infectious dose[TCID]50/mL, strain NADC20). Fecal samples were collected from 48 individual pigs at pre-infection (−2 d post-inoculation [DPI]), peak-infection (10 DPI), and post-infection (144 DPI) timepoints. Extracted DNA was used to quantify fecal microbiota profiles via 16S bacterial rRNA sequencing. Differences in bacterial communities among diet groups were evaluated with principal coordinate analysis and permutational multivariate analysis of variance using UniFrac distance matrices based on both unweighted and weighted UniFrac distances using QIIME 2. All other data were analyzed by one-way ANOVA performed on square root transformations using R. Across all timepoints, only a few differences were observed due to ISF alone mainly in lowly abundant genera. The most notable differences observed were decreased relative abundance of Actinobacteria at 144 DPI between noninfected and infected treatments (P < 0.05), which is consistent with various dysbioses observed in other disease models. Our findings indicate that the differences present were mainly due to PRRSV-infection alone and not strongly influenced by diet, which implies that previously observed performance benefits conferred by dietary ISF are not likely due to the changes in microbiome composition.

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The effect of maternal antibiotic use in sows on intestinal development in offspring

Journal of Animal Science ◽

10.1093/jas/skaa181 ◽

2020 ◽

Vol 98 (6) ◽

Author(s):

Astrid de Greeff ◽

Dirkjan Schokker ◽

Petra Roubos-van den Hil ◽

Peter Ramaekers ◽

Stephanie A Vastenhouw ◽

...

Keyword(s):

Early Life ◽

Antibiotic Use ◽

Fecal Microbiota ◽

Antibiotic Administration ◽

Oral Antibiotic ◽

Intestinal Development ◽

Neonatal Piglets ◽

Tight Junction Formation ◽

Whole Genome Microarray ◽

Morphometry Analysis

Abstract The objective of this study is to investigate the effect of a maternal antibiotic administration during the last week of gestation on the early life intestinal development in neonatal piglets. Colonization of the gut with bacteria starts during birth and plays a major role in the intestinal and immunological development of the intestine. We demonstrate that maternal interventions induced changes in the sows (n = 6 to 8 per treatment) fecal microbiota diversity around birth (P < 0.001, day 1). Whole-genome microarray analysis in small intestinal samples of 1-d old piglets (n = 6 to 8 per treatment) showed significantly expressed genes (Padj < 0.05) which were involved in processes of tight junction formation and immunoglobulin production. Furthermore, when performing morphometry analysis, the number of goblet cells in jejunum was significantly (P < 0.001) lower in piglets from amoxicillin administered sows compared with the respective control piglets. Both significantly expressed genes (Padj < 0.05) and significant morphometry data (jejunum P < 0.05 and ileum P < 0.01) indicate that the crypts of piglets from amoxicillin administered sows deepen around weaning (day 26) as an effect of the amoxicillin administration in sows. The latter might imply that the intestinal development of piglets was delayed by maternal antibiotic administration. Taken together, these results show that maternally oral antibiotic administration changes in early life can affect intestinal development of the offspring piglets for a period of at least 5 wk after the maternal antibiotic administration was finished. These results show that modulation of the neonatal intestine is possible by maternal interventions.

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