Having the wrong bugs in your belly might bugger up your brain

You have trillions and trillions of bacteria living in your intestines. For most of us, most of the time, they do no harm. In fact, quite the opposite. Us and our belly bugs enjoy a symbiotic relationship. We help them, they help us.

Like any other relationship, though, there’s a potential of things going sideways. And when things go bad with the belly bacteria, it can be really bad. Amongst myriad other possible maladies, when symbiosis turns to dysbiosis (an imbalance in the gut microbiome, where there's an increase in harmful bacteria and a decrease in beneficial ones) the brain can really get buggered up.

In 2017, a multinational group of researchers reported that individuals with Alzheimer’s Disease (AD) have lower gut microbe diversity compared to healthy controls. (It may be said that the brain benefits from a good dose of colonic DEI). The study included 25 AD patients and 25 age- and sex-matched healthy controls. Fecal (poop) samples were collected, and gut microbiota composition was analyzed using gene sequencing to assess bacterial diversity. Cerebrospinal fluid (the watery liquid that bathes your brain and spinal cord (CSF)) biomarkers (such as amyloid-beta and tau proteins) and brain imaging (Magnetic Resonance Imaging (MRI)) were used to confirm AD pathology.

AD patients exhibited significantly lower gut microbial diversity compared to controls, indicating dysbiosis. AD patients had decreased abundance of anti-inflammatory, short-chain fatty acid (SCFA)-producing bacteria, such as Bifidobacterium, Butyricicoccus, Clostridium sensu stricto and Faecalibacterium. At the same time researchers have discovered an increased abundance of pro-inflammatory bugs, including Bacteroides and Alistipes in patients suffering from AD.

Just how good are Bifidobacterium?

Bifidobacterium species are beneficial gut bacteria that produce short-chain fatty acids (SCFAs) like butyrate, which have anti-inflammatory properties and support brain health.

In 2022, a Japanese study evaluated the effects of the probiotic Bifidobacterium breve on cognitive function and brain atrophy in older adults with suspected mild cognitive impairment (MCI), a condition often preceding AD. The scientists performed a 24-week randomized, double-blind, placebo-controlled trial, which involved 80 older adults with MCI, based on cognitive screening tests (Mini-Mental State Examination, MMSE). Participants were randomized to receive either Bifidobacterium breve probiotic capsules or a placebo daily for 24 weeks.

The Bifidobacterium breve group showed significant improvements in MMSE scores compared to the placebo group, indicating better cognitive performance, particularly memory-related tasks. MRI analysis revealed a slower rate of hippocampal (a part of the brain involved with memory) volume loss in the probiotic group compared to placebo, suggesting Bifidobacterium exerts a protective effect against brain atrophy.

On the flip side, multiple studies have reported reduced Bifidobacterium levels in AD patients. In addition, there’s an inverse correlation between good bugs and cognitive performance.

Just how bad are Bacteroides?

Bacteroides species, while normal in the intestines, can dominate in dysbiosis. Dysbiosis may increase gut permeability ("leaky gut"), allowing inflammatory molecules to enter the bloodstream and trigger systemic inflammation, which can cross the blood-brain barrier and promote neuroinflammation. Some studies found elevated Bacteroides in AD patients, potentially linked to increased production of pro-inflammatory molecules like lipopolysaccharides (LPS). What’s more, increased Bacteroides abundance has been linked to altered amyloid-beta ratios, suggesting a role in amyloid pathology (amyloid aggregation is a hallmark in brain cells (neurons) afflicted with AD). Before you get too worked up: It’s important to note, the role of Bacteroides is complex. Not all species are harmful and findings vary.

So, what does it all mean?

The bottom line is that bacterial diversity is a marker of a healthy microbiome, and reduced diversity is associated with bad bugs winning out over good ones. The result of the imbalance is increased inflammation and impaired metabolic function. These problems may find their way from the bowel to the brain and are implicated in dementia.

On the bright side, there’s something you might be able to do to help your belly bugs to help your brain. Evidence suggests probiotic supplementation, Bifidobacterium breve, or even dietary changes (e.g., Mediterranean diet) may boost Bifidobacterium. This, in turn, may improve cognitive function and prevent brain atrophy.

Want to learn about microbiome and Alzheimer’s Disease? Check out https://brain2mind.substack.com/p/poop-transplant-and-alzheimers-disease