Contact Us

What is JoVE Visualize?

Emergence of community behaviors in the gut microbiota upon drug treatment

Affiliations
  • 1European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany; European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.
  • 2European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany.
  • 3European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany.
  • 4European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany. Electronic address: kp533@mrc-tox.cam.ac.uk.
  • 5European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany. Electronic address: michael.zimmermann@embl.de.
  • 6European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany; Max Delbrück Center for Molecular Medicine, Berlin, Germany; Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany. Electronic address: bork@embl.de.
  • 7European Molecular Biology Laboratory, Genome Biology, Heidelberg, Germany; European Molecular Biology Laboratory, Structural and Computational Biology, Heidelberg, Germany. Electronic address: typas@embl.de.

|

September 25, 2024

Abstract

Pharmaceuticals can directly inhibit the growth of gut bacteria, but the degree to which such interactions manifest in complex community settings is an open question. Here, we compared the effects of 30 drugs on a 32-species synthetic community with their effects on each community member in isolation. While most individual drug-species interactions remained the same in the community context, communal behaviors emerged in 26% of all tested cases. Cross-protection during which drug-sensitive species were protected in community was 6 times more frequent than cross-sensitization, the converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that the resilience of microbial communities can collapse when perturbations get stronger. By metabolically profiling drug-treated communities, we showed that both drug biotransformation and bioaccumulation contribute mechanistically to communal protection. As a proof of principle, we molecularly dissected a prominent case: species expressing specific nitroreductases degraded niclosamide, thereby protecting both themselves and sensitive community members.

Keywords:

Related Concept Videos

JoVE Research Video for Drugs Affecting GI Tract Motility: Antimicrobials as Antidiarrheal Agents 01:18

47

Acute diarrhea, a common gastrointestinal disturbance, is characterized by the rapid evacuation of fluid stools, leading to an excessive weight in fluid. This condition typically arises from disorders affecting intestinal water and electrolyte transport. It can be triggered by an increased osmotic load within the intestine, excessive secretion of electrolytes and water, mucosal exudation of protein and fluid, or altered intestinal motility. The primary risks of acute diarrhea are dehydration…

JoVE Research Video for Drugs for Treatment of Diarrhea-Predominant IBS 01:17

51

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel…

JoVE Research Video for Drugs Affecting GI Tract Motility: Adsorbents as Antidiarrheal Agents 01:20

63

Diarrhea is characterized by the occurrence of frequent, watery bowel movements. Various factors can trigger diarrhea, including viral or bacterial infections, foodborne illnesses, side effects from certain medications, and underlying digestive disorders. If not adequately managed, diarrhea can lead to complications such as dehydration, electrolyte imbalances, and nutrient deficiencies. Severe diarrhea can lead to significant weight loss, malnutrition, and weakened immune function.
Adsorbents…

JoVE Research Video for Factors Influencing Drug Absorption: Disease States and Pharmacology 01:25

210

Multiple disease states can significantly influence the oral drug absorption process by affecting blood flow and the functionality of the gastrointestinal (GI) system. Various GI diseases, including conditions that alter GI motility, such as diarrhea, decreased acid secretions (achlorhydria), and infections, have been associated with reduced drug absorption.
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,…

JoVE Research Video for Bacterial Flora of the Large Intestine 01:29

251

The gut microbiome is formed by a vast and diverse community of bacteria that colonizes our large intestine. These bacteria start residing in the gut from birth and continue diversifying throughout life, influenced by factors such as diet, lifestyle, and stress. The gut bacterial community also includes bacteria from food and those that enter the colon through the anus.
The normal gut flora of the colon plays a critical role in generating essential vitamins such as vitamins K, B5, and B7.

JoVE Research Video for Drugs Affecting GI Tract Motility: Opioids as Antidiarrheal Agents 01:17

67

Diarrhea, a condition marked by frequent loose or watery bowel movements, can be triggered by multiple factors such as viral or bacterial infections, food intolerances, anxiety, medications, and digestive disorders. Symptoms may include abdominal pain, bloating, nausea, and cramping. Severe or prolonged diarrhea can lead to complications like electrolyte imbalances, malnutrition, and dehydration if left untreated.
Opioids, widely used antidiarrheal agents, mitigate diarrhea by slowing down…