Diarrhea from taking laxatives can alter the microbiome

The findings of this study come as no big surprise to many of us. During the past 10+ years, clinicians and scientists have begun to appreciate the importance of The Microbiome –– all the bacteria that live in our intestine. In fact, if our entire body is ground up and the DNA measured, at least 90-92% of all the DNA is derived from the gut bacteria! The “brain-gut-microbiome” is now recognized as an important interplay between gut bacteria and the central nervous system, with plenty of signals that affect our immune system. Alterations in our intestinal bacteria can alter everything from our mood to increased sensitivity to drugs and risk of various diseases.

Many forms of adversity can affect microbiota colonization and replacement –– yet little is known about how to predict bacterial community response to perturbations and to control reprogramming. Perturbations, such as fever or diarrhea, are perceived as transient. However, temperature (e.g. fever or hypothermia) and osmolality (any solution’s concentration, generally expressed as ‘total number of solute particles’, i.e. ions, chemicals, proteins, lipids, carbohydrates, per kilogram) will induce rapid and drastic changes in microbial physiology. Osmolality is a fundamental property affecting bacterial growth, in which the steady-state growth rate of most bacteria decreasing as the environmental osmolality increases, independent of osmolyte identity. Within a mammalian host (including of course a patient), osmolality is tightly regulated in blood, even if it varies in the intestine because of absorption and secretion of the intestine’s contents and water by epithelial cells lining the intestine.

Osmotic diarrhea is a common medical condition that can arise in a variety of situations (including lactose intolerance and celiac and pancreatic disease). In addition to ‘natural causes’, osmotic diarrhea also can be induced, e.g. osmotic laxatives exploit the inability of the epithelium to absorb either specific compounds (such as polyethylene glycol, PEG) or excessive amounts of solutes (such as salts). These unabsorbed solutes osmotically draw water from the intestinal epithelium into the lumen, leading to increased intestinal motility and decreased stool consistency. Over-the-counter osmotic laxatives are prevalent in the industrialized world; Miralax (PEG with an average molecular weight of 3,350 g/mol) is the second-leading digestive remedy in the U.S. Despite widespread usage and occurrence, current understanding of the impact of osmotic laxatives and osmotic diarrhea on the gut microbiota is limited, hindering the physician in learning how to deal with such problems.

Authors [see attached] assessed the resilience of the gut ecosystem to osmotic perturbation, using mice as a model system. Osmotic stress caused reproducible extinction of highly abundant taxa (groups of populations of organisms –– in this case, bacteria –– seen by taxonomists to form a unit) and expansion of less prevalent members, in the mouse (as well as the human) microbiome. Authors found destruction of the mucus barrier during osmotic perturbation, followed by recovery when osmotic stress is stopped. The immune system exhibited temporary changes in cytokine levels and a lasting immunoglobin-g (IgG) type of immune response against commensal bacteria (i.e. part of the normal gut flora). Environmental availability of microbiota members alleviated these extinction events, demonstrating how species reintroduction can affect gut bacterial community resilience. These data [a] demonstrate that even mild osmotic diarrhea can cause lasting changes to the microbiota and host, and [b] lay the foundation for interventions that might help increase system-wide resilience.


Cell 2o18; 173: 1742–1754

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