Medical Bulletin 27/ June/ 2024

In a study published in Journal Microbiome, researchers from The Jackson Laboratory (JAX) and UConn Health have discovered that sodium valerate, a short-chain fatty acid produced by gut microbes, can dramatically reduce binge drinking behaviour and blood ethanol concentration in mice, offering promising insights into the gut-brain axis and presents a novel therapeutic approach for excessive alcohol use.

Excessive alcohol consumption is a major public health issue, causing numerous health and social problems and imposing a significant economic burden. Alcohol use disorder (AUD) affects approximately 29.5 million people aged 12 and older and often coexists with anxiety disorders. To address this, the FDA has approved medications such as acamprosate, disulfiram, and naltrexone for the treatment of AUD.

Sodium valerate, a derivative of valeric acid, is primarily known for its anticonvulsant and mood-stabilizing properties. It is commonly used in the treatment of epilepsy and bipolar disorder. Recent research suggests it may also have potential therapeutic benefits in reducing binge drinking, highlighting its role in modifying neurotransmitter activity and influencing behaviour related to alcohol consumption.

In a study, researchers investigated the effects of short-chain fatty acid (SCFA) supplementation on alcohol consumption in mice. They found that sodium valerate reduced alcohol intake by 40% and blood ethanol levels by 53%. Molecular changes suggested its potential as a therapy for binge drinking.

Further analyses compared mice given sodium valerate to those given sodium chloride (table salt) as a control. Sodium valerate not only decreased binge drinking but also reduced anxiety-like behaviours. Additionally, increased levels of gamma-aminobutyric acid (GABA), a neurotransmitter linked to alcohol use disorders, were found in the brain, stool, and blood of mice after sodium valerate supplementation.

“The study expands our understanding of the important relationship between the gut microbiome and alcohol consumption. There is strong evidence that binge drinking significantly alters the microbiome in ways that accelerate the cycle of addiction via the gut-brain axis. Our findings provide a possible biological explanation for why that occurs and identify a potential therapy for reducing excessive alcohol use. The implications of our study are significant. By demonstrating how sodium valerate alters gene expression and neurotransmitter levels, we provide a multifaceted explanation for its potential as a treatment for excessive alcohol consumption,” said the researchers.

Reference: Bokoliya, S.C., Russell, J., Dorsett, Y. et al. Short-chain fatty acid valerate reduces voluntary alcohol intake in male mice. Microbiome 12, 108 (2024). https://doi.org/10.1186/s40168-024-01829-6

Consuming fruits, vegetables, and whole grains provides us with healthy dietary fibres.

Researchers from the University of Copenhagen have now found that these fibres are essential in maintaining a balance between the production of beneficial and harmful substances in the colon by influencing bacterial behaviour.

The research, published in the scientific journal Nature Microbiology, revealed that different types of bacteria in our colon compete to utilize the essential amino acid tryptophan, leading to either beneficial or harmful outcomes for our health. The study found that consuming a high amount of dietary fibre helps gut bacteria convert tryptophan into beneficial substances.

Researchers have discovered that dietary fibres, found in fruits, vegetables, and whole grains, not only convert into healthy short-chain fatty acids but also prevent tryptophan from becoming harmful substances, instead promoting its conversion into beneficial compounds. This highlights how dietary fibres influence gut bacteria composition and behaviour, contributing to overall health. Protein-rich foods like chicken, turkey, salmon, eggs, and legumes are key sources of tryptophan, which must be obtained through diet.

Through multiple experiments in bacterial cultures and mice, the researchers demonstrated that fibre-degrading gut bacteria, such as B. thetaiotaomicron, regulate the indole-forming activity of E. coli.

The gut bacterium E. coli can turn tryptophan into a harmful compound called indole, which is associated with the progression of chronic kidney disease. But another gut bacterium, C. sporogenes, turns tryptophan into healthy substances associated with protection against inflammatory bowel diseases, type 2 diabetes, cardiovascular diseases, and neurological diseases.

B. thetaiotaomicron assists by breaking down fibres into simple sugars, which E. coli prefers over tryptophan for growth. The sugar components from the fibres prevent E. coli from turning tryptophan into indole, thereby allowing C. sporogenes to utilize tryptophan to produce healthy compounds.

"These results emphasize that our dietary habits significantly influence the behaviour of gut bacteria, creating a delicate balance between health-promoting and disease-associated activities. In the long term, the results can help us design dietary programs that prevent a range of diseases," said Tine Rask Licht, professor at DTU National Food Institute.

Reference: Sinha, A.K., Laursen, M.F., Brinck, J.E. et al. Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota. Nat Microbiol (2024). https://doi.org/10.1038/s41564-024-01737-3

Dairy isn’t the only food that’s good for bone health. Prunes may also protect bone structure and strength in postmenopausal women, according to a new study led by Penn State researchers.

The findings, published in Osteoporosis International, suggested that daily prune consumption slows the progression of age-related bone loss and reduces the risk of fracture.

Bones are made of dynamic tissues that constantly remodel, with old bone being replaced by new bone. As we age, bone breakdown outpaces bone formation, leading to conditions like osteoporosis. Osteoporosis, affecting over 10 million people according to the CDC, is more common in women and older adults, particularly postmenopausal women. During menopause, declining estrogen levels accelerate bone loss.

While medications exist to treat osteoporosis, many women who need them do not take them. Prunes offer a promising alternative due to their bioactive compounds, like polyphenols, which may reduce inflammation and slow bone loss.

In the study, a 12-month randomized controlled trial was conducted with 235 postmenopausal women to assess the impact of daily prune consumption on bone quality. Participants were divided into three groups: no prunes, 50 grams (four to six prunes) daily, and 100 grams (10 to 12 prunes) daily. Every six months, their bone mass density, bone geometry, and bone strength were measured using peripheral quantitative computed tomography (pQCT).

After one year, women in the control group experienced decreases in bone mass density and bone strength. In contrast, those who consumed at least four to six prunes daily maintained their bone density, bone strength, and bone structure, especially in cortical bone. While both prune groups benefited, the four to six prunes daily regimen was more feasible, as many women in the 100-gram group dropped out due to difficulty incorporating so many prunes into their diet.

"When assessing bone mineral density, we measure the quantity of bone, but we also need to evaluate bone quality. A three-dimensional view reveals bone structure, geometry, and micro-architecture, indicating bone health. Our 12-month study showed that daily prune consumption maintained and preserved the weight-bearing cortical bone of the tibia, which is crucial for preventing fractures. This suggests prunes could potentially reduce the risk of osteoporosis, though more research is needed,” said Mary Jane De Souza, professor of kinesiology and physiology at Penn State.

Reference: Koltun, K.J., Strock, N.C.A., Weaver, C. et al. Prunes preserve cortical density and estimated strength of the tibia in a 12-month randomized controlled trial in postmenopausal women: The Prune Study. Osteoporos Int 35, 863–875 (2024). https://doi.org/10.1007/s00198-024-07031-6