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How poor digestive integrity can cause liver disease
The concept of the “gut-liver axis” is not a new one: it was first described in 1987 when a group of researchers found that patients with cirrhosis had high rates of antibodies in their blood against foods like egg, whey, and casein.
Since that time, the gut-liver-axis has been shown to play a role in the development of most liver diseases, such as cholestatic liver diseases, alcoholic and non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), and even hepatocellular carcinoma (liver cancer). It’s also been shown to play a role in the progression of liver diseases to fibrosis and cirrhosis.
Let’s take a closer look at just how the gut can affect the liver:
Blood flows from the gut to the liver
The liver receives its blood supply from two sources: the hepatic artery and the portal vein. The hepatic artery delivers oxygen-rich blood from the general circulation into the liver, whereas the portal vein – responsible for 70 to 75% of the liver’s blood supply – delivers deoxygenated blood drained from the spleen and the gastrointestinal tract. This post-digestive deoxygenated blood is replete not only in nutrients, but also bacterial products, toxins, and intestinal metabolites.
The liver acts as a secondary “firewall,” protecting the body against the harmful pathogens and other microbial products that may have snuck past the primary barrier of the gut “walls.”
The liver thus not only receives the nourishing nutrients found in the gut, but also, well, its garbage. In this sense, the liver acts as a secondary “firewall,” protecting the body against the harmful pathogens and other microbial products that may have snuck past the primary barrier of the gut “walls.” This, of course, serves in the best interests of the body, but over time taxes the liver.
The leaky gut connection
As explained above, because of portal circulation the liver is the primary recipient of the digestive tract’s “leftovers.” The liver is the first organ to encounter whatever gets past the gut lining, whether it’s helpful nutrients or harmful microbial components. The integrity of the gut can therefore have beneficial or detrimental effects on the liver.
A compromised intestinal barrier (also known as “leaky gut“) allows more harmful substances to pass through the primary barrier of the gut wall, thus increasing the liver’s exposure to microbes and toxins. This phenomenon is known as “metabolic endotoxemia,” a term coined when researchers discovered that even very low levels of gram-negative bacteria translocated from the gut into the bloodstream were involved in triggering the inflammation and insulin resistance responsible for diabetes., This same dysfunction, we now know, can also cause inflammation in the liver: endotoxemia causes a backup of bile flow (known as biliary stasis) at the hepatocellular level, resulting in cellular inflammation and injury.
Intestinal permeability – and the microbe-derived metabolites, secondary bile acids, short-chain fatty acids, and ethanol (alcohol) it shunts to the liver – can thus result in NAFLD and other liver diseases. In fact, it’s been estimated that about 40% of individuals with fatty liver disease have leaky gut, and that hepatic inflammation secondary to endotoxemia has even been shown to be associated with the progression of liver cancer.
About 40% of individuals with fatty liver disease have leaky gut.
The connection between the digestive tract and the liver is not a one-way street, however. The liver can also affect the gut, via the secretion of bile acids and – as those researchers in 1987 discovered – IgA antibodies. The biliary stasis related to endotoxemia thus further contributes to an imbalance of gastrointestinal flora and diminished gastrointestinal motility.
But what causes leaky gut? Although there are many factors – several of which are explored in this piece about leaky gut – perhaps the most pressing cause in the case of liver disease is that of the dysbiosis, an imbalance in the types of bacteria, viruses, fungi, and other microbes found in the gut.
March of the microbes
Multiple independent studies have demonstrated the connection between dysbiosis (microbial imbalance) and several chronic liver diseases – including NAFLD, alcoholic liver disease, cholestatic liver disease, cirrhosis, and even hepatocellular carcinoma.
Alterations in the microbiome, with subsequent leaky gut and liver disease, have also been observed in those with small intestine bacterial overgrowth (SIBO) as well as in those with Helicobacter pylori infection, a common cause of gastric ulcers. The presence of alcohol-producing yeast like Candida albicans or Saccharomyces cerevisiae in the gut have also been associated with fatty liver disease in both adults and children,, and significantly higher levels of blood alcohol have been observed in obese animals.
Building a better, more balanced microbiome is thus a clinically useful approach to both preventing and reversing fatty liver disease. Strategies to improve the microbiome include probiotics, prebiotics, and synbiotics [the combination of prebiotics and probiotics]. In fact, the authors of one study on liver disease highlight their findings with these words: “Modulation of the microbiome by pre-/pro- and synbiotics can deliver significant positive hepatic effects without much concern of major side-effects.”
“Modulation of the microbiome by pre-/pro- and synbiotics can deliver significant positive hepatic effects without much concern of major side-effects.”
Various herbs and natural products can also be used to shift microbial balance, as can strategies to increase stomach acid production. In recent years, more and more research has also emerged around the healing benefits of fecal microbiota transplantation (FMT, or the “poop transplant”).
In fact, FMT has been shown to significantly alter the microbiome and influence health outcomes. In one study, the stool of a patient with severe alcoholic hepatitis was harvested and transplanted into mice. Not only was increased bacterial translocation observed in these mice, but also an increased susceptibility to alcoholic liver damage, more severe liver inflammation, and a higher rate of liver necrosis.
FMT recipients enjoyed better cognitive function and fewer hospitalizations than those who received standard of care (10 vs. 1).
But could receiving FMT with samples gathered from a healthy donor improve outcomes for recipients suffering from liver disease? The answer to this question is presently being researched,,,, but some studies have already demonstrated the promise of FMT. In one such study, stool collected from a donor with a healthy microbiome was transplanted via rectal enema to patients with cirrhosis who had recently completed a five-day course of antibiotic therapy. The participants were then observed for 100 days, a period of time during which the FMT recipients enjoyed better cognitive function and fewer hospitalizations than those who received standard of care (10 vs. 1).
Microbial dysbiosis in the digestive tract goes hand-in-hand with hepatic inflammation, various forms of liver disease, and even liver cancer. By engaging strategies to prevent and heal leaky gut, as well as therapies to build a better microbiome, it may be possible not only to prevent liver disease, but also to reverse it.
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Dr. Erica Zelfand
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