Previous research has established that the health of the gut microbiome is correlated with overall health. According to findings from new research presented at the recent Alzheimer’s Association International Conference, infrequent bowel movements are associated with a greater risk of cognitive decline. In recent studies, researchers identified specific bacteria in the gut microbiome that are correlated with an augmented risk of dementia, as well as gut bacteria that appear to have a neuroprotective effect.

Chronic constipation (CC) is defined as having bowel movements every 3 or more days, and previous research has correlated CC with long-term health issues like inflammation, hormonal imbalances, and anxiety/depression. Research also reveals that nearly 16% of the global population struggles with constipation and that the incidence is even higher among older adults due to age-related factors like fiber-deficient diets, lack of exercise, and using certain constipating drugs to treat other medical conditions.

In a press release, Heather M. Snyder, PhD, Alzheimer’s Association VP of medical and scientific relations, stated, “Our body systems are all interconnected. When one system is malfunctioning, it impacts other systems. When that dysfunction isn’t addressed, it can create a waterfall of consequences for the rest of the body.”

Dr. Snyder also noted, “Still, there are a lot of unanswered questions about the connection between the health of our digestive system and our long-term cognitive function. Answering these questions may uncover novel therapeutic and risk-reduction approaches for Alzheimer’s and other dementias.”

To explore the correlation between cognitive decline and constipation, the Alzheimer’s Association’s project “U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk” (U.S. POINTER), with support from the U.S. National Institutes of Health, is investigating the impact of behavioral interventions on the gut-brain axis to understand better how engaging in healthier habits influences microorganisms in the gut and how variations in gut bacteria relate to brain health.

Dr. Snyder also stated, “While we await the results of the POINTER-Microbiome study, people should talk to their doctor about their digestive health and ways to alleviate constipation, such as increasing dietary fiber and drinking more water. Eating well and taking care of your gut may be a pathway to reduce the risk of dementia.”

To explore this association, Chaoran Ma, MD, PhD, former research fellow at Brigham and Women’s Hospital and Harvard Medical School and current assistant professor at the University of Massachusetts Amherst, evaluated three prospective cohort studies of more than 110,000 people in the Nurses’ Health Study, the Nurses’ Health Study II, and the Health Professionals Follow-up Study. Dr. Ma and team collected data on all of the participants’ bowel movement frequency in 2012 to 2013 and their self-assessments of cognitive function from 2014 to 2017; objective cognitive function was measured between 2014 and 2018 in a subgroup of 12,696 participants.

The researchers discovered that less frequent bowel movements were correlated with poorer cognitive function. Compared with those with bowel movements once daily, constipated participants (bowel movements every 3 days or more) had significantly worse cognition, equivalent to 3.0 years more of chronological cognitive aging. Bowel movement frequency of every 3 days or less was associated with 73% higher odds of subjective cognitive decline. They also discovered a somewhat heightened risk of cognitive decline in those who had bowel movements more than twice a day, and that study participants with certain specific levels of microbes in the gut—fewer bacteria that can produce butyrate and fewer bacteria responsible for digesting dietary fibers—had both less frequent bowel movements and worse cognitive function.

Senior study investigator Dong Wang, MD, ScD, an assistant professor at Harvard Medical School, Brigham and Women’s Hospital, and Harvard T.H. Chan School of Public Health, stated, “These results stress the importance of clinicians discussing gut health, especially constipation, with their older patients. Interventions for preventing constipation and improving gut health include adopting healthy diets enriched with high-fiber and high-polyphenol foods such as fruits, vegetables, and whole grains; taking fiber supplementation; drinking plenty of water every day; and having regular physical activity.”

Mouse models of Alzheimer’s have demonstrated connections between beta-amyloid buildup and levels of specific gut microbiota; however, whether the buildup of Alzheimer’s biomarkers is associated with changes in the human gut microbiota is generally unknown.

To explore this association, Yannick Wadop, PhD, a postdoctoral fellow at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at The University of Texas (UT) Health San Antonio, and colleagues utilized fecal samples and cognitive measures from 140 cognitively healthy middle-aged individuals from the Framingham Heart Study (mean age = 56 years, 54% female) to assess the relationship between gut microbiome composition with amyloid- and tau-positron emission topography measures.

The researchers discovered that elevated levels of amyloid and tau, as detected by brain scans, were correlated with lower levels of gut bacteria Butyricicoccus and Ruminococcus and higher amounts of Cytophaga and Alistipes. The researchers’ functional analysis implied that Butyricicoccus and Ruminococcus may have neuroprotective effects.

Dr. Wadop stated, “These findings begin to reveal more specific connections between our gut and our brain. For example, we believe that the reduction of certain identified bacteria may increase gut permeability and the transport of toxic metabolites in the brain, thus increasing amyloid-beta and tau deposition.”

“One plausible next step is to test whether introducing, increasing, or reducing specific gut microbes might beneficially change levels of amyloid and tau,” Dr. Wadop added. “This could help us identify potential new therapeutic approaches for Alzheimer’s.”

To better comprehend the relationship between the gut microbiome and cognition in middle-aged and older adults, Jazmyn Muhammad, BS, research associate at the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, and colleagues inspected fecal samples and cognitive test scores from more than 1,000 participants in the Framingham Heart Study (average age = 52 years, 55% female).

The researchers divided the study group based on participants’ cognitive test scores and compared the microbiomes of participants scoring in the lowest 20% (i.e., poorer cognition) with those who scored higher. The researchers discovered that individuals with poorer cognition had lower levels of Clostridium and Ruminococcus. In those with poor cognition compared with other study participants, the bacteria Alistipes and Pseudobutyrivibrio were observed to be extremely abundant.

“Further research is needed to better understand the possible neuroprotective effects of some of these bacteria,” Dr. Muhammad stated, “In the future, it may be possible to manipulate the abundance of these bacteria through diet and pre/probiotics to preserve brain health and cognitive function.”

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