From Short- to Long-Term Effects of C-Section Delivery on Microbiome Establishment and Host Health

The establishment of gut microbiota has been proven to be impacted by several factors during pregnancy, delivery, and neonate periods. The body of evidence describing C-section delivery (CSD) as one of the most disruptive events during early life has expanded in recent years, concluding that CSD results in a drastic change in microbiota establishment patterns. When comparing the gut microbiota composition of CSD babies with vaginally delivered (VD) babies, the former show a microbiome that closely resembles that found in the environment and the mother’s skin, while VD babies show a microbiome more similar to the vaginal microbiome. Although these alterations of normal gut microbiota establishment tend to disappear during the first months of life, they still affect host health in the mid–long term since CSD has been correlated with a higher risk of early life infections and non-transmissible diseases, such as inflammatory diseases, allergies, and metabolic diseases. In recent years, this phenomenon has also been studied in other mammals, shedding light on the mechanisms involved in the effects of a CSD on host health. In addition, strategies to revert the disruptions in gut microbiomes caused by a CSD are currently in the process of development and evaluation. In this review, we discuss the recent advances in CSD research, from the alteration of gut microbiota establishment to the possible effects on host health during early life and development.

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Antibiotics at birth and later antibiotic courses: effects on gut microbiota

Pediatric Research ◽

10.1038/s41390-021-01494-7 ◽

2021 ◽

Author(s):

Sofia Ainonen ◽

Mysore V Tejesvi ◽

Md. Rayhan Mahmud ◽

Niko Paalanne ◽

Tytti Pokka ◽

...

Keyword(s):

Gut Microbiota ◽

Control Group ◽

List Type ◽

Antibiotic Exposure ◽

Microbiota Composition ◽

Long Term Effects ◽

The Impact ◽

Antibiotic Courses ◽

Gut Microbiota Composition

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

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Is It Time to Use Probiotics to Prevent or Treat Obesity?

Nutrients ◽

10.3390/nu10111613 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1613 ◽

Cited By ~ 29

Author(s):

Andrea Brusaferro ◽

Rita Cozzali ◽

Ciriana Orabona ◽

Anna Biscarini ◽

Edoardo Farinelli ◽

...

Keyword(s):

Body Weight ◽

Gut Microbiota ◽

Overweight And Obesity ◽

Microbiota Composition ◽

Long Term Effects ◽

Obesity Control ◽

Treatment Of Obesity ◽

Faecal Bacteria ◽

Gut Microbiota Composition

In recent years, attention has been given to the role potentially played by gut microbiota in the development of obesity. Several studies have shown that in individuals with obesity, the gut microbiota composition can be significantly different from that of lean individuals, that faecal bacteria can exert a fundamental role in modulating energy metabolism, and that modifications of gut microbiota composition can be associated with increases or reductions of body weight and body mass index. Based on this evidence, manipulation of the gut microbiota with probiotics has been considered a possible method to prevent and treat obesity. However, despite a great amount of data, the use of probiotics to prevent and treat obesity and related problems remains debated. Studies have found that the probiotic effect on body weight and metabolism is strain specific and that only some of the species included in the Lactobacillus and Bifidobacterium genera are effective, whereas the use of other strains can be deleterious. However, the dosage, duration of administration, and long-term effects of probiotics administration to prevent overweight and obesity are not known. Further studies are needed before probiotics can be rationally prescribed for the prevention or treatment of obesity. Control of the diet and environmental and life-style factors that favour obesity development remain the best solution to problems related to weight gain.

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Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection

mBio ◽

10.1128/mbio.02820-19 ◽

2019 ◽

Vol 10 (6) ◽

Cited By ~ 6

Author(s):

Claire Roubaud-Baudron ◽

Victoria E. Ruiz ◽

Alexander M. Swan ◽

Bruce A. Vallance ◽

Ceren Ozkul ◽

...

Keyword(s):

Gut Microbiota ◽

Bacterial Infection ◽

Early Life ◽

Disease Susceptibility ◽

Antibiotic Exposure ◽

Citrobacter Rodentium ◽

Long Term Effects ◽

Gastrointestinal Microbiota ◽

Content Type

ABSTRACT Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (β-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens. IMPORTANCE The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility.

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Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment

Scientific Reports ◽

10.1038/s41598-020-67271-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Marya Kayyal ◽

Tanvi Javkar ◽

M. Firoz Mian ◽

Dana Binyamin ◽

Omry Koren ◽

...

Keyword(s):

Early Life ◽

Low Dose ◽

Metabolic Diseases ◽

Immune Cell ◽

Male Mice ◽

Long Term Effects ◽

Probiotic Treatment ◽

Relevant Dose ◽

Brain Behavior

Abstract There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received L. rhamnosus JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.

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Melatonin in Early Nutrition: Long-Term Effects on Cardiovascular System

International Journal of Molecular Sciences ◽

10.3390/ijms22136809 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6809

Author(s):

Marie Gombert ◽

Pilar Codoñer-Franch

Keyword(s):

Breast Milk ◽

Cardiovascular System ◽

Infant Health ◽

The Body ◽

Long Term Effects ◽

Melatonin Concentration ◽

Ability To Act ◽

Cellular Environment ◽

Gut Microbiota Composition

Breastfeeding protects against adverse cardiovascular outcomes in the long term. Melatonin is an active molecule that is present in the breast milk produced at night beginning in the first stages of lactation. This indoleamine appears to be a relevant contributor to the benefits of breast milk because it can affect infant health in several ways. The melatonin concentration in breast milk varies in a circadian pattern, making breast milk a chrononutrient. The consumption of melatonin can induce the first circadian stimulation in the infant’s body at an age when his/her own circadian machinery is not functioning yet. This molecule is also a powerful antioxidant with the ability to act on infant cells directly as a scavenger and indirectly by lowering oxidant molecule production and enhancing the antioxidant capacity of the body. Melatonin also participates in regulating inflammation. Furthermore, melatonin can participate in shaping the gut microbiota composition, richness, and variation over time, also modulating which molecules are absorbed by the host. In all these ways, melatonin from breast milk influences weight gain in infants, limiting the development of obesity and comorbidities in the long term, and it can help shape the ideal cellular environment for the development of the infant’s cardiovascular system.

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Obesity, Early Life Gut Microbiota, and Antibiotics

Microorganisms ◽

10.3390/microorganisms9020413 ◽

2021 ◽

Vol 9 (2) ◽

pp. 413

Author(s):

Alyssa T. Wilkins ◽

Raylene A. Reimer

Keyword(s):

Gut Microbiota ◽

Antibiotic Treatment ◽

Early Life ◽

Relevant Literature ◽

Public Health Problem ◽

Current Evidence ◽

Major Public Health Problem ◽

Obesity Risk ◽

Host Health

Obesity is a major public health problem that continues to be one of the leading risk factors for premature death. Early life is a critical period of time when the gut microbiota and host metabolism are developing in tandem and significantly contribute to long-term health outcomes. Dysbiosis of the gut microbiota, particularly in early life, can have detrimental effects on host health and increase the susceptibility of developing obesity later in life. Antibiotics are an essential lifesaving treatment; however, their use in early life may not be without risk. Antibiotics are a leading cause of intestinal dysbiosis, and early life administration is associated with obesity risk. The following review explores the relevant literature that simultaneously examines antibiotic-induced dysbiosis and obesity risk. Current evidence suggests that disruptions to the composition and maturation of the gut microbiota caused by antibiotic use in early life are a key mechanism linking the association between antibiotics and obesity. Without compromising clinical practice, increased consideration of the long-term adverse effects of antibiotic treatment on host health, particularly when used in early life is warranted. Novel adjunct interventions should be investigated (e.g., prebiotics) to help mitigate metabolic risk when antibiotic treatment is clinically necessary.

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Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission

Nutrients ◽

10.3390/nu13082519 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2519

Author(s):

María Juárez-Fernández ◽

Sara Román-Sagüillo ◽

David Porras ◽

María Victoria García-Mediavilla ◽

Pedro Linares ◽

...

Keyword(s):

Bariatric Surgery ◽

Gut Microbiota ◽

Severe Obesity ◽

Short Chain Fatty Acids ◽

Microbiota Composition ◽

Long Term Effects ◽

Efficient Treatment ◽

New Therapeutic Approaches ◽

Gut Microbiota Composition

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.

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Faculty Opinions recommendation of Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733785361.793550849 ◽

2018 ◽

Author(s):

Rino Rappuoli

Keyword(s):

Gut Microbiota ◽

Microbiota Composition ◽

Toll Like Receptor ◽

Toll Like Receptor 5 ◽

Gut Microbiota Composition

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The Neurobiology of Pain

The Oxford Handbook of the Neurobiology of Pain ◽

10.1093/oxfordhb/9780190860509.013.24 ◽

2019 ◽

pp. 387-414

Author(s):

Maria Fitzgerald ◽

Michael W. Salter

Keyword(s):

Early Life ◽

Pain Perception ◽

Long Term Effects ◽

Male And Female ◽

Functional Changes ◽

Pain Pathways ◽

Developmental Age ◽

Short And Long Term ◽

Age And Sex

The influence of development and sex on pain perception has long been recognized but only recently has it become clear that this is due to specific differences in underlying pain neurobiology. This chapter summarizes the evidence for mechanistic differences in male and female pain biology and for functional changes in pain pathways through infancy, adolescence, and adulthood. It describes how both developmental age and sex determine peripheral nociception, spinal and brainstem processing, brain networks, and neuroimmune pathways in pain. Finally, the chapter discusses emerging evidence for interactions between sex and development and the importance of sex in the short- and long-term effects of early life pain.

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