Antibiotics and Gut Microbiota Impact

Consumption of Antibiotics and Microbiota

• Antibiotics have revolutionized infectious disease treatment, increasing life expectancy in the 20th century. However, overuse and misuse in human, veterinary, and animal husbandry have led to widespread antibiotic resistance.
• The gut microbiota plays a vital role in human health, preventing pathogen colonization, regulating gut immunity, providing essential nutrients and bioactive metabolites, and participating in energy homeostasis.
• Broad-spectrum antibiotics can reduce gut microbiota diversity and lead to the eradication of beneficial microbes, alongside killing the pathogens of concern.
• Prenatal and peripartum antibiotic use impacts gut microbial colonization and the microbiome in infants.
• Maternal antibiotic administration during lactation impacts the milk microbiota, affecting infant gut microbial composition.
• Antibiotic-induced changes in microbiota composition have a negative impact on host health, reduce microbial diversity and alter functional attributes of the microbiota.
• Formation and selection of antibiotic-resistant strains occur, making hosts more susceptible to infection with pathogens such as Clostridioides difficile.
• Antibiotic administration directly affects the infant gut microbiota, often leading to alterations, and reduced gut microbiota diversity.
• Premature infants are frequently treated with antibiotics and are among those most impacted by antibiotics.
• Broad-spectrum antibiotics diminish the diversity and richness of gut microbiota. This impact is sustained for up to 12 weeks after antibiotic treatment.
• Bacteriostatic drugs can cause gram-negative bacteria to flourish, related to an increase in LPS synthesis, whereas bactericidal drugs increase gram-positive bacteria and correlate with over-representation of endospore-formation genes.
• Antibiotic administration for Helicobacter pylori eradication can affect the indigenous microbiota and lead to resistant strains persisting for years after treatment.
• Antibiotics are routinely used in dentistry to eliminate pathogens and non-pathogenic strains. This usage can increase the spread of resistant strains.
• Prenatal use of antibiotics can negatively affect the gut microbial composition, impacting immunity, and disease development in later life.

Consequences of Antibiotic-Induced Microbiota Changes

• Links exist between the gut microbiome and modern diseases, such as obesity and juvenile diabetes.
• An increased ratio of Firmicutes to Bacteroides is associated with obesity.
• Significant, persistent weight gain has been associated with episodes of infective endocarditis in patients treated with vancomycin and gentamycin.
• Associations exist between altered microbial composition and type 2 diabetes, showing decreased levels of butyrate-producing bacteria in patients with this condition.
• Antibiotic-associated diarrhea (AAD) is a result of antibiotic-induced changes, demonstrating that clindamycin alters the microbial community and promotes pathogen colonization, like C. difficile, leading to diarrhea and colitis.
• Antibiotic treatment often lowers serotonin, tryptophan hydrolase, and secondary bile acid levels, negatively affecting gut motility and metabolism.

Levels of Serotonin

• Antibiotic treatment can lead to decreased alpha and beta diversities and reduced serotonin, tryptophan hydrolase, and secondary bile acid levels.

During Pregnancy and Infancy

• Extrinsic factors like antibiotics can alter the diversity of the maternal microbiota, impacting infant gut microbiota diversity, and disease development in later life. Both direct and indirect impacts exist.

Immune-Related Disorders

• According to the hygiene hypothesis, lack of exposure to diverse microbiota in early childhood can lead to immune-related disorders like asthma and allergic sensitization.
• Prenatal antibiotic exposure can alter microbial colonization patterns in infant mice and adversely affect CD8+ T lymphocytes toward viral infections and the immune response.

Effect on Colonic Mucus Layer

• Antibiotic treatment can decrease the thickness of the colonic mucus layer, increasing the risk of pathogen invasion and intestinal inflammation.

TH1/TH2 Balance

• Antibiotic-induced alterations in the gut microbiota can shift the TH1/TH2 balance toward TH2-dominant immunity, increasing the risk of atopy development and reducing lymphocyte numbers.

Another Study

• Certain molecules produced by gut bacteria are involved in immune system maturation, with evidence that germ-free mice colonized with B. fragilis producing a polysaccharide (and not non-polysaccharide producing mutant B. fragilis) correctly regulate T-cell deficiencies and improve T (H)1/T(H)2 imbalances along with promoting lymphoid organogenesis.

Antimicrobial Peptides

• Secretion of antimicrobial peptides by intestinal epithelial cells is regulated by the gut microbiota and the microenvironment. Mice exposed to conventional, human or probiotic species (but not solely LPS) showed increased secretion of antimicrobial peptides, as discussed here.

Impact of Antibiotics in Adult Life

• Probiotic use, fecal transplantation and phage therapy are shown to be relevant alternatives to antibiotis treatment that provide ways to restore gut microbial diversity, and prevent damages caused by antibiotic treatments. More research is needed for their use.

Low Dose Antibiotics

• Low-dose or subtherapeutic antibiotic concentrations can disrupt microbial composition, affecting gene expression in immunity, carbohydrate metabolism, metabolic homeostasis, and predisposing the host to adiposity later in life.

Impact on Early Life

• Early antibiotic exposure is associated with a greater risk of asthma, allergy, atopic dermatitis, and inflammatory bowel disease (IBS).

Changes in Immune Response

• The immune system is trained and develops through fighting microbes in early infancy. Any disturbance in early microbial colonization could impact immune maturation in the following development stages.

Effect on Colonic Mucus Layer

• Antibiotic treatment has been observed to lower the thickness of the colonic mucus layer and increase the risk of pathogen invasion in mice.

TH1/TH2 Balance

• Antibiotic-induced alterations change the TH1/TH2 balance toward TH2-dominant immunity, associating microbial composition, and maturation profile changes (including gene downregulation related to MHC class 1b, class II proteins, and Paneth cell products involved in mucosal barrier, such as defensins) in neonatal rats, suggesting the impact on mucosal barriers.

Changes in Metabolites

• The gut microbiota is essential for producing metabolites such as SCFAs and amino acids.
• Studies show that butyrate and propionate from microbiota production have anti-inflammatory effects. Antibiotics can affect the composition of the microbial community and the resulting metabolites produced.

Changes in Protein Expression

• Antibiotic uptake can change protein expression and energy metabolism in the microbiota; this may act as a coping mechanism to the stress the antibiotic poses early in use.

Firmicutes and SCFAs

• Vancomycin and ciprofloxacin-metronidazole treatments result in significant reductions in Firmicutes and SCFAs in female mice; this effect is more strongly seen early post-treatment in females.
• Both antibiotic types significantly decrease levels of alanine, branched-chain amino acids.

Accumulation of Metabolites/Xenobiotics

• Xenobiotics (including antibiotics, heavy metals, and environmental chemicals) impact gut microbial composition in a cyclical manner, depending on the microbiota for biotransformation. Gut microbiota is involved in metabolism of xenobiotics, affecting their half life, their localization, and the host's capacity to metabolize xenobiotics.

Changes in Bacterial Signaling Pathway

• Antibiotics can change the transcription of several key functional genes involved in the transport of proteins, synthesis of carbohydrates, and synthesis of proteins.

Restoring Microbial Community and Betterment of Health.

• Antibiotic-use alters microbial composition, which is detrimental to the host
• Certain strategies may be used along with or after antibiotic therapy to restore and improve the microbial balance more rapidly.

Restoration of Gut Microbiota

• Probiotic use, fecal microbiota transplant (FMT), phage therapy as alternatives to antibiotics
• Bacteriocins have shown potential in improving the gut microbiome through highly targeted specificity.

Conclusion

• Gut microbiota is crucial to host health, influencing metabolism, immunity, and development; Antibiotics can disrupt this intricate balance.
• Clinical management should incorporate careful use of antibiotics, limiting collateral damages, alongside investigating alternatives to treat infections.

References

• Several study references have been included in the original text regarding the importance of antibiotic use on host health.

Additional Notes

• The term for "oral bacteria" was not explicitly used within the provided text.