probiotics
Changes in Human Microbiome Precede Alzheimer’s Cognitive Declines
Posted on by Lawrence Tabak, D.D.S., Ph.D.
In people with Alzheimer’s disease, the underlying changes in the brain associated with dementia typically begin many years—or even decades—before a diagnosis. While pinpointing the exact causes of Alzheimer’s remains a major research challenge, they likely involve a combination of genetic, environmental, and lifestyle factors. Now an NIH-funded study elucidates the role of another likely culprit that you may not have considered: the human gut microbiome, the trillions of diverse bacteria and other microbes that live primarily in our intestines [1].
Earlier studies had showed that the gut microbiomes of people with symptomatic Alzheimer’s disease differ from those of healthy people with normal cognition [2]. What this new work advances is that these differences arise early on in people who will develop Alzheimer’s, even before any obvious symptoms appear.
The science still has a ways to go before we’ll know if specific dietary changes can alter the gut microbiome and modify its influence on the brain in the right ways. But what’s exciting about this finding is it raises the possibility that doctors one day could test a patient’s stool sample to determine if what’s present from their gut microbiome correlates with greater early risk for Alzheimer’s dementia. Such a test would help doctors detect Alzheimer’s earlier and intervene sooner to slow or ideally even halt its advance.
The new findings, reported in the journal Science Translational Medicine, come from a research team led by Gautam Dantas and Beau Ances, Washington University School of Medicine, St. Louis. Ances is a clinician who treats and studies people with Alzheimer’s; Dantas is a basic researcher and expert on the gut microbiome.
The pair struck up a conversation one day about the possible connection between the gut microbiome and Alzheimer’s. While they knew about the earlier studies suggesting a link, they were surprised that nobody had looked at the gut microbiomes of people in the earliest, so-called preclinical, stages of the disease. That’s when dementia isn’t detectable, but the brain has formed amyloid-beta plaques, which are associated with Alzheimer’s.
To take a look, they enrolled 164 healthy volunteers, age 68 to 94, who performed normally on standard tests of cognition. They also collected stool samples from each volunteer and thoroughly analyzed them all the microbes from their gut microbiome. Study participants also kept food diaries and underwent extensive testing, including two types of brain scans, to look for signs of amyloid-beta plaques and tau protein accumulation that precede the onset of Alzheimer’s symptoms.
Among the volunteers, about a third (49 individuals) unfortunately had signs of early Alzheimer’s disease. And, as it turned out, their microbiomes showed differences, too.
The researchers found that those with preclinical Alzheimer’s disease had markedly different assemblages of gut bacteria. Their microbiomes differed in many of the bacterial species present. Those species-level differences also point to differences in the way their microbiomes would be expected to function at a metabolic level. These microbiome changes were observed even though the individuals didn’t seem to have any apparent differences in their diets.
The team also found that the microbiome changes correlated with amyloid-beta and tau levels in the brain. But they did not find any relationship to degenerative changes in the brain, which tend to happen later in people with Alzheimer’s.
The team is now conducting a five-year study that will follow volunteers to get a better handle on whether the differences observed in the gut microbiome are a cause or a consequence of the brain changes seen in Alzheimer’s. If it’s a cause, this discovery would raise the tantalizing possibility that specially formulated probiotics or fecal transplants that promote the growth of “good” bacteria over “bad” bacteria in the gut might slow the development of Alzheimer’s and its most devastating symptoms. It’s an exciting area of research and definitely one worth following in the years ahead.
References:
[1] Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease. Ferreiro AL, Choi J, Ryou J, Newcomer EP, Thompson R, Bollinger RM, Hall-Moore C, Ndao IM, Sax L, Benzinger TLS, Stark SL, Holtzman DM, Fagan AM, Schindler SE, Cruchaga C, Butt OH, Morris JC, Tarr PI, Ances BM, Dantas G. Sci Transl Med. 2023 Jun 14;15(700):eabo2984. doi: 10.1126/scitranslmed.abo2984. Epub 2023 Jun 14. PMID: 37315112.
[2] Gut microbiome alterations in Alzheimer’s disease. Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE. Sci Rep. 2017 Oct 19;7(1):13537. doi: 10.1038/s41598-017-13601-y. PMID: 29051531; PMCID: PMC5648830.
Links:
Alzheimer’s Disease and Related Dementias (National Institute on Aging/NIH)
Video: How Alzheimer’s Changes the Brain (NIA)
Dantas Lab (Washington University School of Medicine. St. Louis)
Ances Bioimaging Laboratory (Washington University School of Medicine, St. Louis)
NIH Support: National Institute on Aging; National Institute of Diabetes and Digestive and Kidney Diseases
Creative Minds: Giving Bacteria Needles to Fight Intestinal Disease
Posted on by Dr. Francis Collins
Cammie Lesser
For Salmonella and many other disease-causing bacteria that find their way into our bodies, infection begins with a poke. That’s because these bad bugs are equipped with a needle-like protein filament that punctures the outer membrane of human cells and then, like a syringe, injects dozens of toxic proteins that help them replicate.
Cammie Lesser at Massachusetts General Hospital and Harvard Medical School, Cambridge, and her colleagues are now on a mission to bioengineer strains of bacteria that don’t cause disease to make these same syringes, called type III secretion systems. The goal is to use such “good” bacteria to deliver therapeutic molecules, rather than toxins, to human cells. Their first target is the gastrointestinal tract, where they hope to knock out hard-to-beat bacterial infections or to relieve the chronic inflammation that comes with inflammatory bowel disease (IBD).
Creative Minds: The Human Gut Microbiome’s Top 100 Hits
Posted on by Dr. Francis Collins
Michael Fishbach
Microbes that live in dirt often engage in their own deadly turf wars, producing a toxic mix of chemical compounds (also called “small molecules”) that can be a source of new antibiotics. When he started out in science more than a decade ago, Michael Fischbach studied these soil-dwelling microbes to look for genes involved in making these compounds.
Eventually, Fischbach, who is now at the University of California, San Francisco, came to a career-altering realization: maybe he didn’t need to dig in dirt! He hypothesized an even better way to improve human health might be found in the genes of the trillions of microorganisms that dwell in and on our bodies, known collectively as the human microbiome.
Eczema Relief: Probiotic Lotion Shows Early Promise
Posted on by Dr. Francis Collins
Caption: Scanning electron microscopic image of Staphylococcus aureus bacteria (orange).
Credit: CDC/Jeff Hageman, MHS
Over the years, people suffering from eczema have slathered their skin with lotions containing everything from avocado oil to zinc oxide. So, what about a lotion that features bacteria as the active ingredient? That might seem like the last thing a person with a skin problem would want to do, but it’s actually a very real possibility, based on new findings that build upon the growing realization that many microbes living in and on the human body—our microbiome—are essential for good health. The idea behind such a bacterial lotion is that good bugs can displace bad bugs.
Eczema is a noncontagious inflammatory skin condition characterized by a dry, itchy rash. It most commonly affects the cheeks, arms, and legs. Previous studies have suggested that the balance of microbes present on people with eczema is different than on those with healthy skin [1]. One major difference is a proliferation of a bad type of bacteria, called Staphylococcus aureus.
Recently, an NIH-funded research team found that healthy human skin harbors beneficial strains of Staphylococcus bacteria with the power to keep Staph aureus in check. To see if there might be a way to restore this natural balance artificially, the researchers created a lotion containing the protective bacteria and tested it on the arms of volunteers who had eczema [2]. Just 24 hours after one dose of the lotion was applied, the researchers found the volunteers’ skin had greatly reduced levels of Staph aureus. While further study is needed to learn whether the treatment can improve skin health, the findings suggest that similar lotions might offer a new approach for treating eczema and other skin conditions. Think of it as a probiotic for the skin!
Creative Minds: Can Microbes Influence Mental Health?
Posted on by Dr. Francis Collins
While sitting in microbiology class as a college sophomore, Elaine Hsiao was stunned to learn that the human gut held between as much as 6 pounds of bacteria—twice the weight of an adult human brain. She went on to learn during her graduate studies in neurobiology that these microbes had co-evolved with humans and played important roles in our bodies, aiding digestion and immune function, for example. But more intriguing to her, by far, was new research that suggested that gut bacteria might even be influencing our thoughts, moods, and behavior.
Now a senior research fellow at the California Institute of Technology, Hsiao is launching her own effort to explore how these microbes can affect brain function—a very creative endeavor made possible through NIH’s Early Independence Award program—also known as the “skip the postdoc” award.
