Impact of Antibiotics on Gut Microbiota

Consumption of Antibiotics and Microbiota

• Antibiotics have revolutionized the treatment of infectious diseases, increasing life expectancy in the 20th century
• Their overuse and misuse in both human and veterinary medicine has resulted in a global antibiotic resistance crisis
• The gut microbiota plays a crucial role in human health, preventing pathogen colonization, regulating gut immunity, providing essential nutrients and bioactive metabolites, and being involved in energy homeostasis
• Broad-spectrum antibiotics can reduce gut microbiota diversity and eradicate beneficial microbes

Learning Objectives

• Students need to understand the relationship between antibiotic consumption and dysbiosis
• Antibiotics affect the gut microbiota, playing a role in gastrointestinal tract (GIT) diseases
• Antibiotic use correlates with the development of multi-drug resistant bacteria
• The impact of antibiotics on the gut microbiota is crucial for host health

Introduction

• Antibiotic-induced changes in microbiota composition have a negative impact on host health, reducing microbial diversity and altering functional attributes
• Such changes can promote the formation and selection of antibiotic-resistant strains, increasing susceptibility to infections such as Clostridium difficile

Impact of 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, impacting the infant gut microbial composition

Impact of Antibiotic Administration Directly on Infant Gut Microbiota

• Premature infants are frequently treated with antibiotics due to health conditions
• Broad-spectrum antibiotics significantly affect the gut bacterial community and early establishment patterns
• This leads to reduced gut microbiota diversity

Impact of Antibiotics on the Gut and Oral Microbiota in Adults

• Changes in microbial composition persist for up to 12 weeks after antibiotic treatment resulting in incomplete restoration and the emergence of resistant strains
• Ciprofloxacin affects the gut microbiota profoundly and rapidly through a decrease in richness and diversity
• By one week after treatment, communities begin to return to their original state

Long-Term Impact on Gut Microbiota

• A short course of clindamycin can result in significant disturbances, inducing a decline in Bacteroides and enterococcal colonies persisting up to two years after treatment

Effect of Different Drugs

• Bacteriostatic drugs may cause a flourishing of Gram-negative bacteria linked to increased LPS synthesis
• Bactericidal drugs are associated with an increase in Gram-positive bacteria often exhibiting over-representation of genes involved in endospore formation

Helicobacter Pylori Eradication and Antibiotics

• Antibiotic administration to eradicate Helicobacter pylori may affect indigenous microbiota, potentially leading to resistant strains persisting for years after treatment

Antibiotics in Dentistry

• Many antibiotics are used routinely in dental procedures
• These antibiotics can increase the number of resistant strains, increase minimum inhibitory concentrations, and eliminate non-pathogenic strains

Consequences of Antibiotic-Induced Microbiota Changes for Health and Disease

• A link between the "missing microbes" and modern conditions like obesity, and juvenile diabetes is present
• An increased ratio of Firmicutes to Bacteroidetes is associated with obesity
• An association between antibiotic-induced microbial colonization changes and type 1 diabetes in male mice has been observed

T2D and Altered Microbial Composition

• Associations between altered microbial composition and type 2 diabetes are well established
• Decreased levels of butyrate-producing bacteria are frequently reported in type 2 diabetic patients

Antibiotic-Associated Diarrhea

• Antibiotic use can lead to antibiotic-associated diarrhea (AAD)
• Clindamycin can alter the microbial community, promoting the colonization of pathogens like C. difficile, leading to diarrhea and colitis

Clostridium Difficile Infection

• C. difficile contains endospores that can survive stomach acidity and reach the large intestine
• C. difficile thrives in the colon producing toxins A and B that cause mucosal damage
• Broad-spectrum antibiotics like clindamycin, cephalosporins, ampicillin, amoxicillin, and fluoroquinolones alter the normal gut flora, making C. difficile flourish

Levels of Serotonin

• Antibiotic treatment leads to decreased alpha and beta diversity, impacting serotonin, tryptophan hydrolase, and secondary bile acid levels
• These changes can further affect gut motility and metabolism

During Pregnancy and Infancy

• Extrinsic factors like antibiotics can alter the maternal microbiota diversity, influencing the infant's gut microbiota, diversity, immunity, and disease development in later life

Immune-Related Disorders

• According to the hygiene hypothesis, if the host is not exposed to a diverse range of microbiota early in childhood, immune-related disorders such as asthma and allergic sensitization might develop.
• Antibiotics administered during infancy can also have a similar effect

Low Dose Antibiotics

• Low-dose or subtherapeutic antibiotic concentrations in early life can disrupt microbial composition and affect the expression of genes (involved in immunity and carbohydrate metabolism) , altering metabolic homeostasis and potentially predisposing the host to adiposity later in life.

Antibiotics, Asthma, Allergy, and IBD

• Antibiotic administration in early life may increase the risk of asthma, allergy, atopic dermatitis, and inflammatory bowel disease (IBD)

Changes in Immune Response

• The immune system is trained during infancy to fight pathogens, with microbial colonization playing a role in this development
• Any disturbance to microbial colonization can affect immune maturation

Effect on Colonic Mucus Layer

• Antibiotic treatment can reduce the thickness of the colonic mucus layer, increasing the risk of pathogen invasion and intestinal inflammation in mice

TH1/TH2 Balance

• Antibiotic-induced alterations in the microbiota shift the TH1/TH2 balance, favouring a TH2-dominant immune response
• This can affect the development of atopy and reduce lymphocyte numbers
• Altered microbial composition and altered gene maturation profile affect MHC class 1b, class II proteins, and Paneth cell products

Another Study

• Certain bacterial molecules in the gut influence immune system maturation, and the presence of these molecules improves T cell function and lymphoid organ development in mice

Antimicrobial Peptides

• Intestinal epithelial cells secrete antimicrobial peptides, which are regulated by the microbiota's microenvironment
• Germ-free mice and mice colonized with specific microbiota demonstrate altered production of antimicrobial peptides such as REGIII-y.

CD8+ Lymphocytes

• Prenatal antibiotics significantly alter the microbiota in infant mice, negatively affecting the activity of CD8+ T lymphocytes against viral infections, affecting immune responses

Influences of Antibiotics on Microbiota: Single-Cell Level

• Antibiotics influence microbiota functionality and bacterial behavior at the single-cell level

Changes in Metabolites

• The gut microbiota is essential for producing metabolites like short-chain fatty acids (SCFAs) and amino acids
• Studies highlight the anti-inflammatory and metabolic roles of butyrate and propionate produced by commensal bacteria.
• Antibiotics can alter microbial community composition, impacting gut metabolite production

Changes in Protein Expression

• Antibiotic uptake might induce changes in protein expression and energy metabolism in the microbiota
• These changes might be a coping mechanism to antibiotic stress, reducing at later stages and post antibiotic use

Firmicutes and SCFAs

• Vancomycin and ciprofloxacin-metronidazole treatments significantly reduce Firmicutes and SCFAs in female mice, particularly after vancomycin administration and in male mice.
• Treatment also decreased branched-chain amino acid levels

Accumulation of Metabolites/Xenobiotics

• Xenobiotics including antibiotics, heavy metals, & environmental chemicals impact gut microbial composition, and vice-versa.
• The microbiota is vital for xenobiotic biotransformation, affecting their metabolism and half-life, which in turn influences the host's xenobiotic metabolization

Changes in Bacterial Signaling Pattern

• Antibiotics alter the transcription of critical functional genes involved in transport proteins, carbohydrate, and protein synthesis in the bacteria

Antibiotic Alternatives and Probiotics

• Probiotics and other alternatives used to restore the microbial community can improve health.

Antibiotic Use vs. Restoration of Microbiota

• Antibiotic use results in microbial composition changes, potentially detrimentally affecting the host
• Strategies exist which include or follow antibiotic treatment to promote faster restoration of the microbial composition

Restoration of Prebiotics and Probiotics

• This section discusses various methods like phage therapy, bacteriocin use, probiotic administration, and monoclonal antibody therapy to potentially restore beneficial gut microbiota composition

Conclusion: Importance of Microbial Interactions

• The gut microbiota is essential for host metabolism and immune function
• Antibiotics disrupt this balance, impacting the bacterial community and host
• Clinical treatment can become difficult due to antibiotic resistance, increasing the need for antibiotics stewardship

This quiz explores the effects of broad-spectrum antibiotics on gut microbiota, particularly in premature infants and adults. Questions cover microbial composition changes, recovery characteristics, and long-term impacts associated with antibiotic use. Test your knowledge on how antibiotics influence gut health!