Medical Bulletin 10/ February/ 2025 - Video

Could the key to easing anxiety be hidden in our gut? Scientists from Duke-NUS Medical School and the National Neuroscience Institute have discovered a crucial connection between gut microbes and anxiety-related behaviour.

Microbial metabolites– specifically indoles–play a direct role in regulating brain activity linked to anxiety, reveals a recent research published in EMBO Molecular Medicine.

The prevalence of mental health disorders has been rising over the years.

The aim of the research was to investigate the role microbes play in anxious behaviour. In pre-clinical studies, the scientists observed that in a germ-free environment, those which were not exposed to live microbes, showed significantly more anxiety-related behaviour than those with typical resident live microbes.

Further investigation revealed that the increased anxiety was associated with heightened activity in a brain region involved in processing emotions such as fear and anxiety, the basolateral amygdala (BLA). This was further identified to be related to specialised proteins within brain cells known as the calcium dependent SK2 channels, associated with anxiety behaviour. In conditions when the body and brain are exposed to live microbe metabolites, the SK2 channels act like a clutch, thus preventing neurons from becoming overly excited and firing too frequently.

Associate Professor Shawn Je from Duke-NUS’ Neuroscience and Behavioural Disorders Programme and one of the lead authors, explained:

“Our findings reveal the specific and intricate neural process that link microbes to mental health. Those without any live microbes showed higher levels of anxious behavior than those with live bacteria. Essentially, the lack of these microbes disrupted the way their brains functioned, particularly in areas that control fear and anxiety, leading to anxious behavior."

The team now hopes to explore clinical trials to determine whether indole-based probiotics or supplements can be effectively used in humans as a natural anxiety treatment. If successful, this could mark the beginning of a new era in mental health care—one where gut microbes help keep our minds at ease.

Ref: Yu W, Xiao Y et al. Microbial metabolites tune amygdala neuronal hyperexcitability and anxiety-linked behaviors. EMBO Mol Med (2025); https://doi.org/10.1038/s44321-024-00179-y

A new drug delivery system shows promise for treating a rare, aggressive form of cancer affecting pregnant women and new mothers, and it has potential with other cancers as well, reports a recent research article published in the Small Science Journal.

Gestational choriocarcinoma (CC) is a rare and highly malignant cancer originating from the trophoblastic layers of the placenta. Currently, methotrexate (MTX) is the first-line treatment for choriocarcinoma (CC); however, due to the aggressive and metastatic nature of choriocarcinoma (CC), multiple doses are often required, leading to severe side effects from the lack of tumour specificity.

Typically starting in the uterus, choriocarcinoma develops from cells that were part of the placenta. It can occur after a miscarriage, abortion or ectopic pregnancy, one in which a fertilized egg implants somewhere other than the lining of the uterus.

It can also happen following a molar pregnancy (no embryo forms, and the placental tissue grows abnormally) and even after a full-term pregnancy.

Taratula and collaborators including OSU postdoctoral researcher Babak Mamnoon and Maureen Baldwin, a physician at Oregon Health & Science University, designed a type of drug nanocarrier known as a polymersome to specifically target a protein in choriocarcinoma cells.

Polymersomes are hollow spheres that are synthetic versions of liposomes, lipid-based sacs found in all living cells. The protein the researchers aimed for is equilibrative nucleoside transporter 1, usually abbreviated as ENT-1, which is important for a range of cellular processes, among them DNA and RNA synthesis.

“Given MTX’s role as the mainstay treatment for choriocarcinoma, the critical goal now is to enhance its effectiveness, including faster response times, while simultaneously minimizing side effects,” said Taratula, an associate professor in the OSU College of Pharmacy.

Most cases, especially if caught early, are curable, with a five-year survival rate of about 87%.

Hence, the authors concluded that the upshot is more effective treatment coupled with fewer or less severe side effects, and with further research, the same approach could be applied to treating other cancers.

Ref: Mamnoon B, Souza APM et al. ENT-1-Targeted Polymersomes to Enhance the Efficacy of Methotrexate in Choriocarcinoma Treatment. Small Science;

https://doi.org/10.1002/smsc.202400361

A recent study involving researchers at Murdoch University’s Health Futures Institute has revealed that moderate-intensity exercise can significantly influence appetite-related hormones and perceptions in males with obesity. The study provides new insights into how exercise can aid appetite control and weight management.

One of the study authors, Associate Professor Timothy Fairchild from Murdoch’s School of Allied Health, said the study confirms their previous work showing the benefits of incorporating regular exercise into daily routines for individuals looking to manage their weight and improve their overall health.

“People understand that exercise helps ‘burn energy’. A lot of people assume that exercise also increases hunger and energy intake afterwards,” Associate Professor Timothy Fairchild said.

“This latest study shows that even moderate-intensity exercise can have immediate and beneficial effects on appetite control in males with obesity.”

The study not only assessed food intake and appetite, but also measured changes in hormones which help to regulate appetite.

Despite a strong focus on weight loss drugs in society at present, this study shows that lifestyle factors still have a strong and relevant role in helping people to live their healthiest life.

In fact, the hormones which have been shown to increase after exercise, are the same hormones which the most successful weight loss drugs are mimicking. The added benefit of exercise is that you also receive the additional physical and mental health benefits of exercise.

Reference:

Sogand Asri, Farhad Rahmani-nia, Payam Saidie, Timothy J. Fairchild, Shahin Khodabandeh, Acute effect of exercise on appetite-related factors in males with obesity: A pilot study, Physiological Reports, https://doi.org/10.14814/phy2.70167