Diarrhea: What Could Be Causing It and What to Do Next

What Exactly Is Diarrhea and How Do Doctors Define It?

Physicians define diarrhea as the passage of three or more loose or watery stools within a 24-hour period, a standard set by the World Health Organization and echoed in clinical gastroenterology guidelines [1]. Stool volume exceeding 200 grams per day is an alternative laboratory criterion. The subjective sense of "going more than usual" without looseness does not meet the diagnostic threshold.

Acute vs. Persistent vs. Chronic

Duration is the first clinical variable that shapes the differential diagnosis.

• Acute diarrhea lasts fewer than 14 days. Infectious causes account for the overwhelming majority of acute cases.
• Persistent diarrhea spans 14 to 29 days and raises concern for parasitic infection, post-infectious irritable bowel syndrome, or early-stage inflammatory bowel disease.
• Chronic diarrhea continues for 30 days or longer. A 2019 review in the American Journal of Gastroenterology found that functional causes (IBS-D and functional diarrhea) accounted for roughly 50% of chronic cases seen in gastroenterology outpatient clinics [2].

How Stool Characteristics Guide Diagnosis

The appearance, frequency, and associated features of stool all carry diagnostic weight.

Watery, large-volume stools without blood typically point to secretory or osmotic mechanisms, including norovirus, enterotoxigenic Escherichia coli, or osmotic laxatives. Small-volume, frequent stools with mucus or blood suggest an inflammatory or invasive process in the left colon or rectum, such as Clostridioides difficile colitis, shigellosis, or ulcerative colitis [3]. Fatty, greasy stools that float signal malabsorption from celiac disease, exocrine pancreatic insufficiency, or giardiasis.

Infectious Causes: Viruses, Bacteria, and Parasites

Infectious agents cause most episodes of acute diarrhea worldwide. The CDC estimates 48 million episodes of foodborne illness occur in the United States each year, resulting in 128,000 hospitalizations and 3,000 deaths [4].

Viral Gastroenteritis

Norovirus is the leading cause of acute gastroenteritis in all age groups in the US, responsible for 19 to 21 million illnesses annually [4]. Rotavirus, now largely preventable by childhood vaccination, remains the top cause of severe diarrheal disease in children under 5 globally. Viral illness typically produces watery diarrhea, vomiting, and low-grade fever that peaks at 24 to 48 hours and resolves within 3 to 5 days without specific therapy.

Bacterial Infections

Bacterial diarrhea follows ingestion of contaminated food or water or direct fecal-oral contact.

Common pathogens include:

• Campylobacter jejuni: the most frequently identified bacterial cause of diarrhea in many high-income countries, often linked to undercooked poultry
• Salmonella spp. (non-typhoidal): associated with eggs, raw meat, and reptile contact
• Shiga toxin-producing E. Coli (STEC), particularly O157:H7: linked to ground beef and produce; can trigger hemolytic uremic syndrome, especially in children
• Clostridioides difficile: the most common healthcare-associated infectious diarrhea, occurring in patients recently treated with antibiotics [5]

A 2020 CDC FoodNet surveillance report confirmed that Campylobacter (19.5 cases per 100,000 population) and Salmonella (17.4 per 100,000) topped bacterial diarrheal pathogens in the US that year [6].

Parasitic Infections

Giardia intestinalis is the most common parasitic cause of diarrhea in developed countries, presenting with 1 to 3 weeks of greasy, malodorous stools, bloating, and fatigue after exposure to contaminated water. Cryptosporidium causes profuse watery diarrhea, particularly dangerous in immunocompromised individuals. Entamoeba histolytica causes amebic dysentery and is seen more often in travelers returning from tropical regions.

Non-Infectious Causes in Outpatient Practice

A large share of diarrhea evaluated in primary care is not infectious. These cases are frequently misattributed to "a stomach bug" when the actual driver is a medication, a functional disorder, or an inflammatory bowel condition.

Medication-Induced Diarrhea

More than 700 drugs list diarrhea as a potential adverse effect. The most clinically significant include:

• Antibiotics: broad-spectrum agents (clindamycin, fluoroquinolones, third-generation cephalosporins) disrupt the gut microbiome and are the primary precipitant of C. Difficile infection [5].
• Metformin: causes diarrhea in 10 to 53% of patients starting therapy; extended-release formulations reduce this rate to roughly 10% [7].
• GLP-1 receptor agonists: In the SUSTAIN-6 trial (N=3,297), semaglutide 0.5 mg and 1.0 mg weekly produced diarrhea in 22.1% and 21.7% of participants, respectively, vs. 12.7% and 12.5% on placebo [8]. Symptoms usually peak during dose escalation and taper over 4 to 8 weeks.
• Laxative overuse (including sorbitol-containing sugar-free foods): osmotic mechanism, stops when the agent is removed.
• NSAIDs and proton pump inhibitors: may alter intestinal motility and microbiome composition.

Irritable Bowel Syndrome with Predominant Diarrhea (IBS-D)

IBS-D is a functional gut-brain disorder characterized by chronic abdominal pain relieved by defecation and altered stool form without structural abnormality. The Rome IV diagnostic criteria require symptom onset at least 6 months prior and recurrent abdominal pain at least 1 day per week for the preceding 3 months [9].

Prevalence in North America is approximately 10 to 15% of the general population. A 2021 meta-analysis in Gut (pooling 73 studies, N=349,231) estimated global IBS prevalence at 9.2% using Rome IV criteria [10]. Diarrhea-predominant subtype accounts for roughly one-third of IBS cases.

Inflammatory Bowel Disease

Crohn's disease and ulcerative colitis frequently present with chronic or relapsing diarrhea. Ulcerative colitis characteristically produces bloody, mucoid stool with urgency and tenesmus. Crohn's disease produces more variable stool output depending on the segment affected and may include periumbilical cramping, weight loss, and perianal disease.

The American Gastroenterological Association (AGA) states: "Chronic diarrhea with blood, nocturnal symptoms, or unexplained weight loss should prompt evaluation for inflammatory bowel disease with colonoscopy and biopsy" [3].

Celiac Disease and Malabsorption

Celiac disease affects approximately 1% of the US population, though up to 83% remain undiagnosed [11]. Chronic, often fatty diarrhea combined with bloating, iron-deficiency anemia, or unexplained weight loss should trigger serologic screening with tissue transglutaminase IgA (tTG-IgA) antibodies plus total serum IgA [11].

Exocrine pancreatic insufficiency (EPI) produces steatorrhea and diarrhea after meals, typically in patients with a history of chronic pancreatitis, cystic fibrosis, or prior pancreatic surgery. Fecal elastase-1 below 200 mcg/g stool confirms EPI [12].

Microscopic Colitis

Microscopic colitis (collagenous and lymphocytic subtypes) is an underdiagnosed cause of chronic, watery, non-bloody diarrhea, particularly in women over 50 and individuals taking NSAIDs, proton pump inhibitors, or SSRIs. The colon appears grossly normal at colonoscopy; diagnosis requires mucosal biopsy. Incidence in the US is 7 to 10 cases per 100,000 person-years [13].

Traveler's Diarrhea

Traveler's diarrhea (TD) affects 20 to 50% of international travelers, with risk highest in South Asia, sub-Saharan Africa, and parts of Latin America [14]. Enterotoxigenic E. Coli (ETEC) is responsible for 30 to 40% of TD cases. Symptoms typically begin 4 to 14 days into travel and last 3 to 5 days.

The CDC 2024 Yellow Book advises that prophylactic antibiotics are generally not recommended for most travelers but that rifaximin 200 mg three times daily for up to 14 days may be used for high-risk itineraries. Oral rehydration is the primary management. Azithromycin 1,000 mg single dose (or 500 mg daily for 3 days) is the preferred empirical antibiotic for moderate-to-severe TD outside South Asia [14].

How Is Diarrhea Diagnosed?

History and Physical Examination

Most acute cases require no laboratory testing. The clinical history should establish duration, stool frequency and character, associated symptoms (fever, vomiting, blood), recent antibiotic or medication changes, travel history, dietary exposures, and sick contacts. The physical exam focuses on hydration status: skin turgor, mucous membrane moisture, heart rate, and orthostatic blood pressure.

When Laboratory Testing Is Indicated

The ACG Clinical Guideline on Acute Diarrhea in Adults (2016, updated 2023) recommends stool cultures, ova-and-parasite examination, or C. Difficile testing only when [15]:

• Diarrhea persists beyond 7 days
• Blood or mucus is present in stool
• Fever exceeds 38.5 C
• The patient is immunocompromised or returned from international travel
• There is a potential public health (outbreak) concern

Multiplex PCR-based stool panels (e.g., BioFire FilmArray GI Panel) detect 22 pathogens simultaneously and have sensitivity exceeding 90% for most targets, though their role in routine care is debated due to cost and the clinical relevance of co-detections [15].

Workup for Chronic Diarrhea

Chronic diarrhea (30 days or longer) warrants a structured evaluation that typically includes:

1. Complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and C-reactive protein or erythrocyte sedimentation rate
2. Serologic celiac screening (tTG-IgA + total IgA)
3. Fecal calprotectin (elevated in IBD; typically below 50 mcg/g in functional diarrhea)
4. Colonoscopy with biopsies if red flags are present or if initial labs are unrevealing

The HealthRX clinical team uses a three-axis framework for chronic diarrhea workup: (1) exclude structural and inflammatory causes first (colonoscopy, fecal calprotectin), (2) screen for malabsorptive causes second (tTG-IgA, fecal elastase), and (3) apply functional diagnoses like IBS-D only after organic pathology has been ruled out with appropriate specificity.

Treatment: What Actually Works

Oral Rehydration

Replacing fluid and electrolytes is the cornerstone of diarrhea management at all ages. The WHO/UNICEF oral rehydration solution formula (75 mEq/L sodium, 75 mmol/L glucose, 20 mEq/L potassium, total osmolarity 245 mOsm/L) reduces the need for intravenous hydration by approximately 30% in adults with cholera and by up to 64% in children with non-cholera diarrhea compared to higher-osmolarity solutions [16]. Sports drinks are not ORS equivalents. Gatorade contains roughly 21 mEq/L sodium, well below therapeutic targets.

Antimotility Agents

Loperamide 4 mg loading dose followed by 2 mg after each loose stool (maximum 16 mg/day) reduces stool frequency and shortens duration of acute watery diarrhea in adults without fever or blood. A 2020 Cochrane review (17 trials, N=1,894) found that loperamide reduced the duration of acute diarrhea by approximately 1.2 days compared to placebo [17]. Loperamide is contraindicated in bloody diarrhea and suspected C. Difficile infection.

Antibiotics: Narrow Indications

Empirical antibiotics are not recommended for most acute diarrhea. Specific indications include confirmed or highly suspected shigellosis (azithromycin 500 mg daily for 3 days), C. Difficile infection (fidaxomicin 200 mg twice daily for 10 days is preferred over vancomycin 125 mg four times daily for 10 days per IDSA 2021 guidelines [18]), or moderate-to-severe traveler's diarrhea.

Giving antibiotics for undifferentiated diarrhea may prolong Salmonella carriage, increase C. Difficile risk, and promote antimicrobial resistance. The IDSA guidelines state: "Empiric antibiotic therapy is not recommended for most community-acquired diarrheal illness in immunocompetent adults" [18].

Probiotics

Evidence for probiotics in acute diarrhea is modest. A 2020 Cochrane review of 82 randomized trials found that Lactobacillus and Saccharomyces boulardii preparations reduced acute diarrhea duration by approximately 25 hours vs. Placebo [19]. The effect was more pronounced in children than adults. Clinical guidelines do not uniformly recommend them, citing heterogeneity in strain, dose, and preparation.

IBS-D-Specific Therapies

For IBS-D, rifaximin 550 mg three times daily for 14 days produced meaningful relief of global IBS symptoms and bloating in 40.7% of patients vs. 31.7% on placebo (P<0.001) in the TARGET-1 and TARGET-2 trials (combined N=1,258) [20]. Eluxadoline 100 mg twice daily reduces bowel urgency and pain in patients without prior cholecystectomy. Alosetron 0.5 mg twice daily is FDA-approved for women with severe IBS-D who have not responded to conventional therapy.

When Should You Worry? Red Flags That Require Urgent Care

Most diarrheal illness is self-limiting. Seek same-day or emergency evaluation for any of the following:

• Blood in stool (maroon or bright red) or black, tarry stool
• Fever at or above 38.5 C (101.3 F) lasting more than 24 hours
• Signs of severe dehydration: dizziness on standing, decreased urine output, confusion, or heart rate above 100 bpm at rest
• Diarrhea persisting beyond 7 days without improvement
• Recent antibiotic use (within the past 3 months) combined with watery or mucoid diarrhea, suggesting C. Difficile
• Immunocompromised status (HIV, chemotherapy, biologic therapy, organ transplant)
• Age over 70 with moderate-to-severe symptoms
• Diarrhea in an infant under 6 months old

The American College of Gastroenterology notes that "passage of more than 10 stools per day or dehydration significant enough to require intravenous fluids in the emergency department warrants inpatient evaluation regardless of etiology" [15].

Diarrhea in Special Populations

Children Under 5

Diarrhea is the second leading cause of death in children under 5 globally, accounting for approximately 484,000 deaths in 2022 (WHO) [1]. Rotavirus vaccination (RV1 or RV5, given at 2 and 4 months, with an optional third dose at 6 months depending on formulation) reduces rotavirus-associated hospitalizations by 59 to 91% in high-income countries [4]. Oral rehydration and zinc supplementation (10 to 20 mg daily for 10 to 14 days) are the WHO-recommended treatment pillars for childhood diarrhea.

Older Adults

Older adults face disproportionate risk from C. Difficile, medication-induced diarrhea, and microscopic colitis. Fecal impaction with overflow incontinence mimics true diarrhea in institutionalized patients and can be missed without a rectal examination.

Immunocompromised Patients

Patients on immunosuppression require a broader infectious workup including cytomegalovirus (CMV) colitis, Cryptosporidium, Microsporidium, and Mycobacterium avium complex. A CD4 count below 200 cells/mcL in HIV disease is associated with opportunistic enteric infections [18].