Medical Bulletin 11/ June/ 2024

In a recent study published in the journal Clinical Nutrition ESPEN, researchers explored causal associations between the gut microbiome and paediatric adiposity.

Childhood adiposity is a growing concern, associated with numerous health issues in both children and adults. Childhood obesity is significantly influenced by genetics, environment, lifestyle, and gut flora. While lifestyle factors like diet and exercise play a crucial role, the causal relationship between adiposity and gut microbes remains unclear.

Gut microbes affect obesity by altering host metabolism, with studies noting imbalances in bacteria such as Clostridium and Eubacterium among individuals prone to obesity. The proposed gut-brain axis suggests that treatments like faecal microbiota transplantation and prebiotic supplementation could be potential anti-obesity strategies.

In the study, researchers employed Mendelian randomizations (MR) to investigate the causal association between gut microbes and childhood obesity. The study involved 32 children, with 16 classified as obese and 16 without adiposity.

Researchers assessed their weight, body mass index (BMI), abdominal circumference (AC), serum lipid levels (triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and high-density lipoproteins (HDL)), and gut microbiomes. Participants also provided faecal samples for genetic sequencing.

The children, aged nine to twelve years, had no history of thyroid or liver-related diseases, congenital disorders, or genetic defects, and had not yet reached puberty. Obese children underwent a three-month weight reduction intervention, which included calorie restrictions and increased physical activity. To validate the impact of obesity on gut flora, researchers examined the gut flora macro-genes before and after the weight reduction intervention in obese participants.

Using Mendelian randomization, researchers identified 16 causal associations between gut microbes and pediatric adiposity. The results revealed five significant differences in intestinal microbes between obese participants and those without adiposity. Notably, the team observed increased abundances of Romboutsia, Turicibacter, and Clostridium following weight reduction in obese children.

The findings highlighted that gut microbes produce various compounds during digestion, such as short-chain fatty acids (SCFAs), which influence adipogenesis and hormone synthesis. Reduced gut microbial diversity may increase insulin resistance and levels of pro-inflammatory markers. Obesity-related bacteria contribute to the development of obesity by affecting host energy balance and central hunger regulation through gut-brain interactions.

Reference: Lu M, Feng R, Li M, Liu L, Xiao Y, Liu Y, Yin C, Causal relationship between gut microbiota and childhood obesity: a Mendelian randomization study and case-control study, Clinical Nutrition ESPEN, DOI: 10.1016/j.clnesp.2024.05.012, https://www.sciencedirect.com/science/article/pii/S2405457724001311

An artificial sweetener known as sugar alcohol might not be as healthy as it sounds.

In a study published in the European Heart Journal, researchers from the Cleveland Clinic found that higher amounts of xylitol, a type of sugar alcohol, can increase the risk of heart attack, stroke, and other cardiovascular events.

As a type of sugar alcohol, xylitol occurs naturally in small amounts in fibrous fruits and vegetables, corn cobs, trees, and even the human body. It is commonly used as a sugar substitute because it tastes similar to sugar but has fewer calories. Found in a variety of products such as sugar-free candy, gum, and toothpaste, xylitol is also frequently used as a sweetener and in baking.

Research has discovered that over the past decade that sugar substitutes such as sugar alcohols and artificial sweeteners have significantly increased in processed foods promoted as healthy alternatives.

In the study, researchers analysed more than 3,000 subjects and revealed that high levels of circulating xylitol were associated with an elevated three-year risk of cardiovascular events. A third of the subjects with the highest amount of xylitol in their plasma were more likely to experience a cardiovascular event.

The research team further conducted pre-clinical testing to confirm these findings and discovered that xylitol caused clotting in platelets and heightened the risk of thrombosis. Additionally, the researchers tracked platelet activity in subjects who ingested a xylitol-sweetened drink versus a glucose-sweetened drink.

They found that every measure of clotting ability significantly increased immediately following the ingestion of xylitol, but not glucose.

“Based on this study, it is thought that xylitol affects the ‘stickiness’ of platelets in the bloodstream, potentially increasing the risk of forming a blood clot in the heart or in the brain. This heightened activity could raise the risk of clots forming unexpectedly, potentially leading to cardiovascular events like heart attack or stroke. This study adds another chapter to the evolving story of sugar substitutes and heart health. In recent years, there has been a growing awareness that these alternatives might not be as risk-free as once believed,” said the authors.

Reference: Marco Witkowski, Ina Nemet, Xinmin S Li, Jennifer Wilcox, Marc Ferrell, Hassan Alamri, Nilaksh Gupta, Zeneng Wang, Wai Hong Wilson Tang, Stanley L Hazen, Xylitol is prothrombotic and associated with cardiovascular risk, European Heart Journal, 2024;, ehae244, https://doi.org/10.1093/eurheartj/ehae244

A recent study published in Nature Communications suggested the statin drug, Pitavastatin, could help suppress chronic inflammation and prevent pancreatic cancer development. If future research confirms the findings, this drug could be a preventive measure in clinical practice.

Cancer prevention is a major field of research, and experts are continuing to learn more about what factors may contribute to cancer development. One area of interest is how chronic inflammation in certain areas of the body may contribute to cancer risk.

Statins are typically prescribed to help lower cholesterol levels in people whose “bad” cholesterol levels are too high. Statins can be used in combination with lifestyle changes to help keep cholesterol in a healthy range. For example, people may minimise their saturated fat intake and increase their physical activity levels.

In the study, researchers noted that interleukin 33 (IL-33) is a protein that helps initiate cancer-prone chronic inflammation. Utilizing mice, human tissue samples, and cell lines, they induced chronic inflammation in the skin and pancreas of mice.

They discovered that IL-33 was highly expressed in these inflamed areas. Further analysis revealed that inflammation activation triggered a specific signaling pathway which may cause the IL-33 expression seen in chronic inflammation.

Researchers then tested the use of pitavastatin to block IL-33 expression, finding that it may successfully inhibit IL-33 expression and related chronic pancreatitis.

Lastly, researchers looked at electronic health records from over 200 million people to look at the use of pitavastatin and the risk for pancreatic cancer and discovered that people taking pitavastatin were at a decreased risk for chronic pancreatitis and pancreatic cancer.

“Approximately 15-20% of cancer deaths worldwide are linked to cancers arising from chronic inflammation. We aimed to identify what triggers chronic inflammation in various organs. Discovering that interleukin 33 (IL-33) drives this type of inflammation, we investigated the cellular mechanism behind its expression. Our study shows how a statin drug can block IL-33 expression, preventing chronic inflammation and cancer in experimental models. Interestingly, statin use in patients, primarily for high cholesterol, is associated with a reduced risk of pancreatitis and pancreatic cancer,” said study author Shadmehr Demehri.

Reference: Park, J.H., Mortaja, M., Son, H.G. et al. Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression. Nat Commun 15, 4099 (2024). https://doi.org/10.1038/s41467-024-48441-8