Medical Bulletin 14/ June/ 2024

A recent study published in the journal Scientific Reports reported the potentially pathogenic changes in oral microbiota following the consumption of sugar-rich drinks.

The oral microbiome consists of over 700 species of bacteria, along with various other microorganisms. Disruption of this microbiome is linked to oral diseases and may also contribute to diabetes, cardiovascular disease, and some cancers.

Saliva is commonly used to study the oral microbiome because it is easily accessible and stable, reflecting changes due to other microbiomes or external factors. Researchers in the current study aimed to determine the impact of sugary drinks, such as soft drinks and fruit juices, on salivary microbiota. The high acidity and sugar content of these drinks can lead to tooth decay and support bacteria that thrive in acidic environments, which in turn can produce more acid from carbohydrates.

In the study, oral wash samples were collected from 989 participants who were healthy at baseline. Each participant provided saliva samples and completed a food frequency questionnaire to assess their dietary intake over the past year. The sugary drinks evaluated included orange or grapefruit juice, 100% fruit juices or mixtures, and other sugary beverages like lemonade and soft drinks.

In a separate cohort, participants reported their consumption of soda, other caffeinated beverages, lemonade, punch, iced tea, and various fruit juices. In both groups, fructose and sucrose from these drinks served as sources of fermentable sugar in their diets.

The results showed that the highest consumption of sugary beverages among participants was 336 and 398 grams per day, equivalent to more than one can of juice or soda daily. Males, smokers, non-diabetics, and those with higher calorie intake were more likely to consume these high amounts of sugary drinks.

Higher consumption of sugary beverages was linked to lower α-diversity richness of salivary microbial species. Additionally, a greater intake of sugar-rich drinks was associated with an increased relative abundance of microorganisms such as Bifidobacteriaceae.

The findings suggested that increased sugary drink consumption is linked to reduced bacterial richness and altered oral microbiome composition, with a higher abundance of acid-producing bacteria and fewer commensals.

The reduced richness may decrease the microbiome's stability and resilience, predisposing individuals to diseases. This could result from the harmful effects of high-sugar and high-acid drinks or impaired oral health.

Reference: Fan, X., Monson, K. R., Peters, B. A., et al. (2024). Altered salivary microbiota associated with high-sugar beverage consumption. Scientific Reports. doi:10.1038/s41598-024-64324-w.

In a systematic review published in the journal Frontiers in Nutrition, researchers conducted a comprehensive assessment of the role of antioxidants in mitigating female reproductive complications induced by high-fat diets.

These diets, abundant in saturated and trans fats, are known to generate reactive oxygen species (ROS) that induce oxidative stress. This oxidative stress disrupts the female reproductive system by causing irregular ovulation, premature ovarian failure, impairing blood flow to reproductive organs, and disrupting the hypothalamic-pituitary-ovarian axis. Consequently, hormonal imbalances, insulin resistance, and inflammation can affect oocyte quality and compromise pregnancy maintenance.

Biological matrices containing antioxidants such as carbocyclic sugars, phytonutrients, organosulfur compounds, hormones, neuropeptides, organic acids, and vitamins have been identified as potential countermeasures against ROS-induced damage.

The systematic review involved an analysis of data from 121 studies to evaluate the effectiveness of these biological matrices in preventing ovarian complications resulting from high-fat diet-induced oxidative stress.

The analysis highlighted that components like carbocyclic sugars, phytonutrients, organosulfur compounds, and vitamins play crucial roles in enhancing ovarian follicle resilience, improving oocyte quality, and extending reproductive lifespan. Moreover, in vivo studies using mammalian preclinical models demonstrated the efficacy of antioxidants derived from biological matrices in alleviating conditions induced by high-fat diets.

Specifically, high-fat diets impair ovarian follicle development, survival, and hormone production, thereby affecting oocyte quality and embryo development negatively. However, in rodent models, dietary interventions incorporating phytonutrients from barley and dates have shown promise. These interventions preserved ovarian follicles, stimulated their development and proliferation, restored ovarian tissue integrity, and elevated endogenous antioxidant levels.

The research also indicated that antioxidants derived from biological sources effectively reduced the incidence of atretic follicles, mitigated ovarian inflammation, and minimized ovarian cell death. This was observed by changes in ovarian weight, reduction in peri-ovarian fat deposits, and modulation of LH receptor activity, suggesting potential therapeutic benefits for managing reproductive health under conditions of oxidative stress induced by high-fat diets.

Reference: Berardino CD. 2024. High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices. Frontiers in Nutrition. https://www.frontiersin.org/articles/10.3389/fnut.2024.1415455/full

A large study conducted by researchers at Stanford Medicine, published in New England Journal of Medicine, has found that the risk of secondary blood cancers after CAR-T cell therapy — a cell-based cancer treatment for intractable blood cancers — is low.

CAR-T cell therapy is an advanced treatment for certain types of cancer. It works by harnessing the body's immune system to fight cancer cells. In the therapy, doctors collect a patient's T cells, genetically modify them to recognize and attack cancer cells, and then infuse these modified cells back into the patient. Once inside the body, these supercharged T cells target and destroy cancer cells, effectively treating the cancer.

In November 2023, the FDA issued a warning about a risk of secondary cancers — particularly blood cancers — that may be associated with CAR-T cell therapy. The warning was preceded by rising concern following reports of patients diagnosed with T cell cancers unrelated to the cancer for which they had been treated.

However, a study involving over 700 patients treated at Stanford Health Care found that the risk of developing a second cancer after CAR-T cell therapy is low, about 6.5% over three years. The researchers used molecular, cellular and genetic analyses to compare all 724 patients’ tumours, their CAR-T cells and their healthy cells at multiple time points before and after CAR-T cell treatment.

The analysis found no evidence that the T cells responsible for the patient’s second cancer were the T cells engineered for the CAR-T cell therapy — they were molecularly and genetically distinct. However, both sets of T cells were infected with a virus known to play a role in cancer development.

In the only instance where a secondary T-cell cancer was fatal, researchers determined it was likely caused by the weakened immune system from CAR-T cell therapy. This allowed existing cancer cells, which were not previously identified, to grow rapidly in the patient's body.

The study’s findings suggested that secondary cancers appearing after CAR-T cell therapy might result from the immune system being weakened before treatment or from the side effects of the therapy itself.

“These findings highlight the importance of studying immune suppression before and after CAR-T cell therapy to understand its role in cancer risk. As CAR-T treatments expand beyond high-risk blood cancers to conditions like autoimmune diseases, this study provides a framework to evaluate their outcomes and clarify their risks and benefits. While CAR-T therapies are lifesaving with minimal risk of secondary cancers, predicting which patients might face higher risks remains a challenge,” said the study authors.

Reference: Emily Mitchell, George S. Vassiliou; T-Cell Cancer after CAR T-Cell Therapy, New England Journal of Medicine, 390, 22, (2120-2121), (2024); /doi/full/10.1056/NEJMe2405538