`Constipation is a common complication in chronic kidney disease (CKD) patients and has been identified as the third most common symptom among patients with end-stage kidney disease (ESKD). Recent studies have reported a higher prevalence of constipation in dialysis patients than in healthy controls. Mounting evidence suggests that gut dysbiosis may be a common link between constipation and CKD progression.*

What is gut dysbiosis?

The human gastrointestinal (GI) tract harbors trillions of microbes, primarily bacteria. The diversity and abundance of this microbe community are closely related to your body’s ability to:

• Digest complex dietary macronutrients 
• Produce vitamins and other nutrients 
• Protect against pathogens
• Regulate your immune system 

The makeup of gut microbiota is different for each person, is shaped early in life, and is influenced throughout the life course by:

• Age
• Ethnicity 
• Lifestyle
• Dietary habits 

When a microbial imbalance occurs, and the gut lacks sufficient beneficial bacteria, the condition is called gut dysbiosis.

Causes of gut dysbiosis

Scientists think that CKD-related gut dysbiosis may be facilitated by:

• Dietary restriction of fiber-rich foods
• Intake of multiple medications
• Build-up of uremic toxins

When the number of bacteria that produce harmful uremic toxins expands, it overpowers the bacteria that produce beneficial short-chain fatty acids, such as butyrate. Gut-derived uremic toxins (GDUTs) cause oxidative stress and inflammation, while butyrate has an anti-inflammatory effect and contributes to gut epithelial health. 

How gut dysbiosis relates to constipation in CKD

Studies show that gut dysbiosis may relate to constipation in several ways. 

Fermentation in the colon

A significant portion of uremic toxins is produced by bacterial protein fermentation in the colon. CKD hinders the digestion and absorption of proteins. Dietary fiber helps with protein absorption. With fiber intake restricted, a larger amount of proteins reaches the colon, and the resulting toxins degrade the mucus layer that aids the passage of stool.

Disruption of the gut epithelial barrier

Studies also show that urea, ammonia, and uric acid impair the gut epithelial barrier (a layer of cells that protects the gut), slowing the movement of the digestive system. Gut epithelial edema (swelling) and intestinal ischemia (inadequate blood supply), resulting from hypotension during and after hemodialysis (HD) sessions can exacerbate the situation. 

Pathogenic, or disease-causing, factors

Inflammation plays an important role in the slow movement of the GI tract. 

In two separate rodent studies: 

• CKD rats showed significantly decreased intestinal motility after undergoing a 5/6 nephrectomy (surgical removal of one or both kidneys).
• CKD mice showed gut dysbiosis, intestinal dysmotility, reduced fecal amount, and intestinal inflammation. Antibiotic therapy improved intestinal dysmotility.

Potential treatments for gut dysbiosis-related constipation

Treatments for constipation focus on inducing regular bowel movement, improving stool consistency, resolving incomplete evacuation, reducing harmful uremic toxins, and optimizing the gut’s microbial composition. 

Common interventions include:

• Probiotics, prebiotics, and synbiotics: Probiotics are live microorganisms present in some foods and also taken as supplements. Prebiotics are indigestible food components, such as dietary fiber and resistant starches. Synbiotics are combinations of probiotics and prebiotics administered together. Some studies suggest that synbiotics may have the most beneficial effect, but that can depend on the probiotics and prebiotics used.
• Diet: Multiple dietary restrictions have been recommended for CKD patients, especially for people on dialysis. However, these restrictions reduce the intake of beneficial vitamins, minerals, and dietary fiber and can worsen hypertension, hyperphosphatemia, and metabolic acidosis. Using certain cooking methods, like soaking and boiling, can help increase fiber intake and decrease potassium load. 
• Formulations of short-chain fatty acids (SCFAs): These have beneficial effects, but they have an unpleasant taste and odor, making them difficult to administer orally. Further studies are also needed on their clinical effects to establish the safety of their administration.
• Fecal microbiota transplantation (FMT): This procedure has been found to improve colonic transit time, stool frequency, and stool consistency, but the procedure is complex, and the cost is prohibitive. 
• Laxatives: Laxatives add bulk to stool and speed up the movement of the digestive tract. They’re the go-to treatment for constipation, though the American Gastroenterological Association (AGA) only recommends them for temporary use.
• Removal of GDUTs: The primary harmful GDUTs cannot be adequately removed by the intermittent nature of conventional HD. Patients may benefit from combining HD with therapies that inhibit uremic toxin production.
• Exercise therapy: Higher levels of physical activity and cardiorespiratory fitness have been positively associated with bacterial diversity in patients’ stools, improvement of physical function and restless leg syndrome, and other benefits. 

CKD-related constipation is often difficult to treat and control due to its multifactorial nature. Further research is necessary to help develop additional treatment options.

*Ikee, R., Sasaki, N., Yasude, T., & Fukazawa, S. (2020, Dec.). Chronic Kidney Disease, Gut Dysbiosis, and Constipation: A Burdensome Triplet. Microorganisms. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760012/