What is antibiotic-associated diarrhea?

from Sebastian Moll February 6, 2025

Antibiotics are essential for the treatment of bacterial infections, but they do not exclusively target pathogens. Rather, they also influence the symbiotic, complex community of the intestinal microbiota. Especially in animals—and especially in dogs—this can lead to significant gastrointestinal side effects. So-called antibiotic-associated diarrhea is the result of a multifactorial disorder attributable to the direct and indirect effects of antibiotics. In addition to the altered microbial composition, direct toxic effects on the intestinal mucosa and immunological changes also play a role.

1. Effects of antibiotics on the intestinal microbiota

1.1 Normal function of the intestinal flora

The intestinal microbiota consists of a variety of bacteria, archaea, viruses, and fungi that maintain a symbiotic relationship with the host. In dogs, these microorganisms perform essential functions, such as:

Fermentation of dietary fiber: This produces short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate, which serve as an energy source for colonocytes and contribute to the maintenance of the mucosal barrier.
Immune system regulation: The microbiota supports the development and function of the immune system by influencing the balance between pro- and anti-inflammatory signals.
Protection against pathogens: By competing for nutrients and spatial occupation, symbiotic bacteria prevent the overgrowth of opportunistic pathogens.

1.2 Antibiotic-induced dysbiosis

Antibiotics, especially broad-spectrum antibiotics, can disrupt this finely balanced community, a process known as dysbiosis . Studies such as those by Suchodolski et al. (2009) and Garcia-Mazcorro et al. (2012) have shown that even short-term antibiotic treatment leads to a significant loss of bacterial diversity. The consequences are:

Loss of protective bacteria: The decline in bacteria that produce SCFAs weakens the intestinal mucosa.
Overgrowth of opportunistic germs: Bacteria such as certain Clostridium species can grow in this ecological “vacuum,” leading to increased production of toxic metabolites.
Altered metabolic processes: Fermentation and the breakdown of nutrients are impaired, which can lead to osmotic diarrhea, as undigested substances in the intestinal lumen attract water.

2. Pathophysiological mechanisms of antibiotic-associated diarrhea

2.1 Dysbiosis and metabolic consequences

Antibiotic-induced dysbiosis has several immediate consequences:

Reduced SCFA production: SCFAs such as butyrate are not only important energy sources but also signaling molecules that regulate cellular metabolism and intestinal mucosal repair. A decrease in these metabolites weakens the mucosa and impairs nutrient and water absorption.
Osmotic effects: Food components that are not fully fermented or digested have an osmotic effect and draw water into the intestinal lumen, leading to watery diarrhea.

2.2 Direct toxic effects

Some antibiotics have an intrinsic mucosal irritant effect:

Direct irritation of the intestinal mucosa: At high doses or with prolonged use, antibiotics can damage the epithelial cells of the gastrointestinal tract. This leads to a local inflammatory reaction, increased release of fluid and electrolytes, and ultimately diarrhea.
Study reference: Weese (2003) documents in his review article that such direct effects often occur in combination with microbial changes.

2.3 Immunomodulation and inflammatory reactions

Antibiotics can affect the balance of the local immune system:

Immunological shifts: A disturbed microbiota can lead to altered cytokine production, creating a local pro-inflammatory environment.
Consequences for the intestinal mucosa: The resulting inflammation can further weaken the integrity of the mucosa and aggravate diarrhea.

3. Differences between antibiotic-associated diarrhea and other forms of diarrhea

3.1 Temporal relationship and clinical course

Antibiotic administration as a trigger: Antibiotic-associated diarrhea often occurs in direct temporal association with the medication. It usually begins shortly after the start of antibiotic therapy and is often observed as a transient phenomenon that resolves with the end of treatment or through adaptation of the microbiota.
Comparison with infectious diarrhea: In viral or bacterial infections (e.g., Salmonella, Campylobacter), the onset of diarrhea is often independent of medication and may be accompanied by systemic symptoms such as fever and fatigue. Infectious diarrhea can also be more intense or chronic.

3.2 Pathophysiological differences

Mechanisms: While infectious diarrhea is often caused by direct cell damage and toxin production by the pathogens, antibiotic-associated diarrhea is primarily caused by disruption of the symbiotic intestinal flora.
Bacterial diversity: Modern molecular biological techniques (e.g., 16S rRNA sequencing) have shown that antibiotic-induced diarrhea is characterized by a general loss of bacterial diversity, whereas other forms of diarrhea often show an overgrowth of individual pathogenic species.

3.3 Clinical manifestation and severity

Symptoms: Antibiotic-associated diarrhea is often mild to moderate and usually self-limiting. However, other causes such as inflammatory bowel disease or infectious agents can lead to a more severe or even chronic condition.
Additional symptoms: Infectious diarrhea is often accompanied by systemic symptoms (e.g., fever, lethargic state), whereas antibiotic-associated diarrhea often occurs in isolation.

4. Other influencing factors and individual variability

4.1 Type and dosage of the antibiotic

Broad-spectrum vs. narrow-spectrum antibiotics: Broad-spectrum antibiotics, which eliminate a wider range of microorganisms, generally have a stronger impact on the intestinal microbiota, increasing the risk of significant dysbiosis.
Duration of therapy: Prolonged antibiotic administration promotes more lasting disruption of the microbiota, while short therapies often lead to only temporary changes.

4.2 Individual factors of the dog

Age and pre-existing conditions: Younger animals or dogs with existing gastrointestinal problems are often more sensitive to changes in the microbiota.
Genetic predisposition: Genetic factors can influence the composition of the intestinal flora and the response to antibiotics.
Nutrition: A balanced diet rich in prebiotics can support the resilience of the gut microbiota and reduce the risk of diarrhea.

4.3 Interactions with other medications

Combination therapies: The simultaneous administration of medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) can increase the damaging effects on the intestinal mucosa and promote diarrhea.

5. Scientific sources and further reading

Suchodolski, J.S., et al. (2009).
The effect of antibiotics on the fecal microbiome of healthy dogs.
Journal of Veterinary Internal Medicine, 23(3), 463-467.
doi :10.1111 /j .1939 -1676.2009.0322 .x
– Shows the influence of antibiotics on the composition of the fecal microbiota in dogs.
Garcia‐Mazcorro, JF, et al. (2012).
Dysbiosis in fecal microbial communities of dogs with acute diarrhea.
FEMS Microbiology Letters, 337(2), 131–137.
doi :10.1111 /j .1574 -6968.2012.02583 .x
– Investigates the relationship between dysbiosis and acute diarrhea.
Weese, JS (2003).
Antimicrobial therapy and the gastrointestinal tract.
Veterinary Clinics of North America: Small Animal Practice, 33(6), 1233-1244.
doi :10.1016 /j .cvsm .2003.08.006
– Discusses direct toxic effects of antibiotics on the gastrointestinal tract.
Bartlett, JG (2002).
Clinical practice. Antibiotic-associated diarrhea.
New England Journal of Medicine, 346(5), 334-339.
doi :10.1056 /NEJMcp011991
– Provides insights into the mechanisms of antibiotic-associated diarrhea in humans, which are also transferable to dogs.
Guard, RM (2009).
The intestinal microflora and gastrointestinal diseases in dogs and cats.
Veterinary Clinics of North America: Small Animal Practice, 39(1), 19-41.
doi :10.1016 /j .cvsm .2008.09.007
– Overview of the relationship between gut microbiota and gastrointestinal diseases in dogs.
Jergens, A.E., et al. (2010).
Alterations of the intestinal microbiota in dogs with antibiotic-responsive enteropathy.
Journal of Veterinary Internal Medicine, 24(5), 1074-1079.
doi :10.1111 /j .1939 -1676.2010.0618 .x
– Shows how changes in the microbiota are related to specific enteropathic conditions.
Suchodolski, JS (2011).
Understanding the canine intestinal microbiota and its modification by pro-, pre-, and synbiotics – what is the evidence?
Veterinary Clinics of North America: Small Animal Practice, 41(2), 261-272.
doi :10.1016 /j .cvsm .2010.12.002
– A further overview of the influence of external factors, including antibiotics, on the intestinal microbiota.

6. Summary and conclusions

Antibiotic-associated diarrhea in dogs is a complex phenomenon primarily caused by disruption of the symbiotic intestinal microbiota. Antibiotic-induced dysbiosis leads to:

Reduced production of protective metabolites (e.g. SCFAs), which are essential for the maintenance of the intestinal mucosa.
Osmotic effects , as undigested food components draw water into the intestinal lumen.
Direct toxic effects that lead to irritation and damage to the mucous membrane.
Immunomodulatory changes that promote a pro-inflammatory environment.

These mechanisms differ significantly from those in infectious or inflammatory forms of diarrhea, which are often caused by specific pathogens or chronic inflammatory processes. While antibiotic-associated diarrhea often occurs in close temporal association with medication and usually improves after discontinuation of the antibiotic, other forms of diarrhea can exhibit more severe and prolonged clinical courses.

The available scientific studies underline that a thorough understanding of the interactions between antibiotics and the intestinal microbiota is of great importance not only for veterinary practice but also for the development of future therapeutic strategies.