Antibiotics and Gut Health in Infants

Consumption of Antibiotics and Microbiota

• Antibiotics have revolutionized infectious disease treatment, increasing life expectancy in the 20th century. However, overuse and misuse have led to a global antibiotic resistance crisis.

Learning Objectives

• Students need to understand the relationship between antibiotic consumption and dysbiosis.
• Students need to know the role of antibiotics in gastrointestinal (GI) tract diseases.
• Students need to understand the role of antibiotics in multi-drug resistant bacteria colonization.

Introduction

• Antibiotic-induced changes in microbiota composition negatively impact host health.
• These changes result in reduced microbial diversity and altered functional attributes of the microbiota.
• The formation and selection of antibiotic-resistant strains increase host susceptibility to infections like Clostridioides difficile.

Antibiotics

• Antibiotics have transformed the treatment of infectious diseases.
• Their widespread use has increased life expectancy in the 20th century, but excessive use in humans, veterinary medicine, and animal husbandry has also led to the global antibiotic-resistance crisis.

Impact of Broad-Spectrum Antibiotics on the Gut Microbiota

• Broad-spectrum antibiotics can kill a wide variety of bacteria, including beneficial ones, impacting gut microbiota.
• The gut microbiota has a fundamental role in human health by preventing pathogen colonization, regulating gut immunity, providing essential nutrients, and involved in energy homeostasis.

In Infants

• Infant gut microbiota is acquired at birth and plays a key role in gut immunity.
• A properly balanced microbiota composition with diverse species is crucial for optimal gut function.
• Reduced diversity and imbalance of the infant gut microbiota are associated with intestinal illnesses and increased susceptibility to future diseases.

Impact of broad-spectrum antibiotics during pregnancy and lactation

• Perinatal and peripartum antibiotic use can impact gut microbial colonization and the microbiome in infants.
• Maternal antibiotic administration during lactation influences the milk microbiota, affecting the infant gut microbial composition.

Impact of antibiotic administration directly to infants on the infant gut microbiota

• Premature infants often receive antibiotics due to health conditions.
• Broad-spectrum prophylactic antibiotics affect a large proportion of the gut bacterial community.
• This disruption can lead to alterations in the initial establishment pattern that results in reduced gut microbiota diversity.

Diagrammatic Representation of the Effect of Various Antibiotics on Human Gut Bacteria

• Diagram displays the impacts of various antibiotics (e.g., clindamycin, penicillin) on the human gut bacteria.
• Green indicates increasing levels of bacteria; red indicates decreasing levels.

Impact of Antibiotics on the Gut and Oral Microbiota in Adults

• Changes in microbial composition persist for up to 12 weeks after antibiotic treatment.
• Incomplete restoration of microbial composition and new emergence of antibiotic-resistant strains are common.
• The effect of ciprofloxacin on the gut microbiota is profound and rapid with decreased richness and diversity, with shifts in the levels of Bacteroidetes, Lachnospiraceae, and the Ruminococcaceae.

Long-Term Impact of Antibiotics on Gut Microbiota

• Short-term antibiotic courses, such as clindamycin (7 days), can cause significant disturbances, such as sharp declines in Bacteroides and enterococcal colonies.
• These disturbances often persist for up to two years post-treatment.

Effect of Different Drugs

• Bacteriostatic drugs lead to the flourishing of Gram-negative bacteria related to an increase in LPS genes involved in LPS synthesis.
• These drugs are accompanied by an increased presence of genes involved in endospore formation among Gram-positive bacteria.

Helicobacter Pylori and Antibiotics

• Antibiotic treatment for the eradication of Helicobacter pylori can affect the indigenous microbiota, potentially leading to the development of resistant strains that can persist for years after treatment.

Antibiotics Used in Dentistry

• Many antibiotics are routinely used in dentistry.
• The overuse of antibiotics can increase the number of resistant strains.
• Antibiotics concentration present within the oral cavity can raise minimum inhibitory concentration, eliminate non-pathogenic strains.

Consequences of Antibiotic-Induced Microbiota Changes for Health and Disease

• Antibiotics affect the gut microbiota and associated diseases like obesity, type 1 diabetes and others.
• This disruption can have long-term effects on host metabolism and immune function.

T2D

• Altered microbial composition and reduced levels of butyrate-producing bacteria are associated with type 2 diabetes.

AAD

• Antibiotic Use can lead to antibiotic associated diarrhea (AAD).
• Studies demonstrate that clindamycin can alter the microbial community and cause the colonization potential of pathogens like C. difficile, which can leads to diarrhea and colitis.

Clostridium Difficile Infection

• C. difficile infection is caused by antibiotics.
• It produces toxins A and B, causing mucosal damage resulting in Pseudomembranous colitis (yellowish plaques over damaged epithelium).

Levels of Serotonin

• Antibiotic treatments can decrease levels of serotonin, tryptophan hydrolase, and secondary bile acids, potentially impacting gut motility and metabolism.

During Pregnancy and Infancy

• Extrinsic factors like antibiotics can alter maternal microbiota diversity affecting the infant's gut microbiota, potentially impacting the diversity, immunity, and disease development.

Immune-Related Disorders

• Disorders such as asthma and allergic sensitization can result from a lack of diverse microbiota exposures in early childhood, consistent with the hygiene hypothesis.
• Prenatal antibiotics can negatively alter the pattern of microbiota colonization, and affect CD8+ T cell activity which is crucial for immune response to viral infections.

Low Dose Antibiotics

• Low or subtherapeutic antibiotic concentrations can lead to changes in microbial composition, influencing various biological processes (e.g., immunity, carbohydrate metabolism) thus affecting metabolic homeostasis and predisposing the host to adiposity.

Firmicutes and SCFAs

• Vancomycin and ciprofloxacin-metronidazole treatment can reduce levels of Firmicutes and SCFAs in female mice, specifically after vancomycin treatment.
• Exposure to both antibiotics can also decrease levels of branched-chain amino acids.

Accumulation of Metabolites and Xenobiotics

• Xenobiotics (like antibiotics, heavy metals) can impact gut microbial composition, affecting xenobiotic biotransformation and metabolism, and influencing host capacity.
• This interaction is cyclical: xenobiotics alter microbial composition, which, in turn, affects xenobiotic metabolism.

Changes in Bacterial Signaling Patterns

• Antibiotics may alter transcriptional activity in several major functional bacterial genes which can lead to metabolism regulation, protein and carbohydrate synthesis changes.

Antibiotic Alternatives and Probiotics

• Probiotics can be used to restore the microbial community and improve health after antibiotic consumption.

Restoration of Prebiotics and Probiotics

• Strategies to restore prebiotics and probiotics are vital in optimizing gut health by targeting and restoring resistance of gut microbiota following antibiotic consumption.

Conclusion

• Gut microbiota is essential in host metabolism, immunity, and colonization.
• Antibiotics disrupt the microbial balance, affecting gut-host networking.
• Techniques like prebiotics and probiotics support a quicker restoration of the microbe and gut ecosystem.
• Resistant bacteria produced by antibiotic treatment pose additional challenges for clinical treatment.
• Careful antibiotic stewardship and the use of antibiotic alternatives is necessary.