“Our bodies have a finely tuned, built-in detoxifying system: It’s called our liver, and it can detoxify our bodies better than any cleanse or fast.” —Harley Pasternak

The community of microbes in our gut, like any other neighborhood, requires a trash service. Some wastes, like ammonia, can build up in our gut and make life uncomfortable for both us and our microbes. Fortunately, our liver continually sweeps the ammonia up, repackages it as urea, and sends it off to our kidneys to pee out. Problem solved.

But if the liver is badly damaged and can’t take out the trash, then the ammonia will build up in the body, including the brain. That’s bad news. Although the damage is mostly temporary, it is often not subtle. It can lead to confusion, disorientation, erratic behavior, mood swings, hallucinations, and personality changes. It’s not new. Hippocrates wrote that his advanced liver patients were the worst: combative and noisy.

This is hepatic encephalopathy (HE), and it can be devastating. A common precursor is cirrhosis, the leading cause of liver-related mortality. Although alcohol is a major contributor to cirrhosis, recent research has shown that there is a microbial aspect to it as well. The gut microbiome is disturbed in cirrhosis patients, producing toxins that may exacerbate the disease.

Almost half of all cirrhosis patients go on to develop HE. If untreated, half of those patients won’t live out the year.

You might think a liver transplant would be called for, but people with HE are considered high risk and put on the back burner. Instead, as we’ll see, there’s another kind of transplant that may help.

What causes hepatic encephalopathy?

The gut-microbiome-liver-brain axis.

Source: Scott Anderson

We have long known that HE is a disease that straddles the gut-microbe-liver-brain axis. In fact, the microbial angle to HE was discovered when doctors realized that antibiotics could improve its symptoms. By killing ammonia-producing microbes, antibiotics deal with the trash at the source. However, as is often the case with antibiotics, it can create a lot of collateral damage to beneficial bacteria.

A less destructive treatment involves probiotics. These can help balance the gut microbiome to favor more fastidious microbes that produce less ammonia. Still, some HE patients are unable to totally renew their microbiome and can suffer relapses.

So it’s welcome news that a new treatment from a team in Virginia has a good success rate treating recurring HE. Led by Jasmohan Bajaj, the researchers at Virginia Commonwealth University used a fecal microbiota transplant (FMT), which is just as icky as you’re probably imagining. However, what FMT lacks in glamour, it totally makes up for in efficacy.

FMT is the last resort for fixing the gut microbiome. Unlike antibiotics, which kill indiscriminately, or probiotics, which aim to supplement the existing microbiome, FMT aims for dominance and permanent occupation. That’s called engraftment, and of all the probiotic options, it’s the nuclear one.

Within just a couple of days of their FMT, patients who seemed hopelessly impaired became their old selves again. Their brain fog lifted, and they were happier.

Fecal capsules (crapsules)

Source: Midjourney AI art generator

The small clinical study found that it didn’t matter much which end was used for the transplant; both enemas and oral capsules (inevitably called “crapsules”) were successful. But enemas seemed to engraft better than capsules. That’s important, because the better the engraftment, the more enduring the outcome.

The treatment was almost five times more successful than placebo in treating recurring HE.

As an interesting side note, there were two fecal donors. One was a vegan and the other an omnivore, and both of their donations were equally successful.

How does fecal microbiota transplant work?

How does the FMT fix cognition problems and psychosis? It starts in the gut. An unbalanced microbiome can lead to a leaky gut, allowing bacteria and toxins to enter the bloodstream. The heart dutifully pumps these marauders to every organ in the body, including the brain.

The brain is a pampered organ that is walled off from the rest of the body by the blood-brain barrier (BBB)—designed to let nutrients in and keep toxins out. That includes ammonia. But if the gut is chronically leaky, it can lead to systemic inflammation. Like the death of a thousand cuts, that slowly breaks down the BBB. Ammonia released from the gut can then enter the brain, where it causes cellular damage to various brain tissues, bringing about mood, cognition, and personality changes.

Inflammation also exacerbates the already diseased liver, which further impairs its ability to clean up microbial detritus, sustaining a vicious cycle.

FMT breaks this cycle by introducing anti-inflammatory microbes like Bifidobacteria, Lachnospira, and Ruminococcus. These bacteria produce butyrate, a marvelous molecule that is both food and medicine for the gut lining. These new microbes also help to displace the ammonia-producing microbes, improving the neighborhood.

Psychobiotic

Technically, that makes these microbes psychobiotics—bacteria that can improve mood and cognition.

This example of the gut-brain axis is somewhat extreme but proves the basic point that the state of the brain is, for better or worse, connected to gut microbes—in this case, someone else’s microbes.

The ordinary gut-brain connection is not quite as dramatic, involving depression and anxiety more than psychotic behavior. But the takeaway is consistent: If you want a clear head, treat your gut well.

That means plenty of veggies and fermented foods. It brings me no joy to tell you this, but alcohol is a double-whammy, making the gut leakier while also stressing the liver.

As Hippocrates pointed out: “Let food be your medicine and medicine be your food.” Eat right and prosper. Otherwise, one day you may need to prepare for the nuclear option.