Medical Bulletin 02/December/2025

Infertility is defined as the failure to conceive after 12 months of regular unprotected sexual intercourse and can lead to significant psychological distress and social stigma. The WHO guideline includes 40 evidence-based recommendations that cover all stages of infertility care, focusing on cost-effective prevention and treatments that are respectful of patients’ needs and preferences.

It emphasizes investing in education on fertility and risks such as age, untreated sexually transmitted infections, and tobacco use—encouraging lifestyle changes like healthy diet, physical activity, and smoking cessation to improve reproductive outcomes.

The guideline proposes a stepwise clinical approach for diagnosis and treatment. Initial management includes counseling on fertile windows and fertility promotion without medical treatment. For diagnosed infertility, it recommends progressing to treatments like ovulation induction, intrauterine insemination (IUI), and, if necessary, assisted reproductive technologies such as in vitro fertilization (IVF).

Recommendations are tailored to patient age and cause of infertility — for example, surgery may be suggested for mild tubal disease in younger women, while IVF is preferred for severe cases or older patients. The guideline also advises against unnecessary advanced treatments like intracytoplasmic sperm injection (ICSI) without clear indication.

WHO underscores the importance of integrating psychosocial support throughout fertility care to address depression, anxiety, and social isolation commonly experienced by patients. The guideline advocates for fertility care to be part of comprehensive sexual and reproductive health programs guided by principles of gender equality, reproductive rights, and informed choice.

Acknowledging existing research gaps, WHO plans future guideline updates to include fertility preservation, third-party reproduction, and the influence of pre-existing health conditions. This comprehensive framework seeks to reduce global infertility inequities, empower individuals with informed reproductive decisions, and ensure affordable, dignified care worldwide.

REFERENCE: Guideline for the prevention, diagnosis and treatment of infertility; World Health Organization; 2025; https://www.who.int/publications/i/item/9789240115774

Hidden blood molecules found to have powerful anti-aging effects in skin cells

Scientists have discovered promising anti-aging compounds produced by a little-known blood bacterium, opening a new frontier for skin rejuvenation. These naturally occurring molecules, called indole metabolites, were shown to reduce inflammation, oxidative stress, and collagen degradation in human skin cells cultured in the lab.

The findings, published in the Journal of Natural Products, suggest these blood-derived metabolites could provide innovative skin-aging therapies.

The bacterium, Paracoccus sanguinis, was first identified in 2015 and is unique because it lives within the bloodstream—a relatively unexplored area for microbial metabolic activity. Researchers Chung Sub Kim, Sullim Lee, and their team grew large cultures of P. sanguinis over three days and extracted the full mixture of metabolites it produces.

Using techniques like spectrometry, isotope labeling, and computational analysis, they characterized 12 distinct indole metabolites, six of which were previously unknown.

To test their anti-aging potential, the team exposed human skin cells to stress that elevates reactive oxygen species (ROS), molecules known to cause inflammation and collagen damage—key drivers of skin aging. They then treated the cells with each indole metabolite in liquid form.

Among the 12 compounds, three (including two newly identified metabolites) effectively reduced ROS levels compared to untreated samples. These three also lowered two inflammatory proteins and a collagen-damaging protein called MMP-1 in the skin cells.

One standout metabolite, referred to as metabolite 11, showed the highest efficacy in protecting the skin cells, making it a promising candidate for future clinical applications in skincare.

This study sheds light on the untapped potential of blood-borne microbes like P. sanguinis, whose metabolites may offer natural, potent defenses against the biochemical processes behind skin aging.

While more research is needed to translate these findings to safe and effective treatments, this discovery opens exciting avenues for developing next-generation anti-aging products based on the body's own microbiome and its unique metabolites.

REFERENCE: Won Min Lee, Si-Young Ahn, Gyu Sung Lee, InWha Park, Jonghwan Kim, Seung Hwan Lee, Sullim Lee, Chung Sub Kim. Discovery and Biosynthesis of Indole-Functionalized Metabolites from the Human Blood Bacterium, Paracoccus sanguinis, and Their Anti-Skin Aging Activity. Journal of Natural Products, 2025; 88 (5): 1120 DOI: 10.1021/acs.jnatprod.4c01354

Study reveals Chronic drinking disrupts blood-brain barrier via the gut

Chronic alcohol consumption quietly destabilizes one of the brain’s most vital defenses—the blood-brain barrier (BBB)—through disruptions in the gut-brain axis, leading to cognitive decline.

Researchers explored this link in a recent study published in Communications Biology, investigating whether the gut microbiome changes caused by alcohol use disorder (AUD) directly impair BBB integrity and whether a probiotic, Faecalibacterium prausnitzii, could restore brain health.

The BBB protects the brain by restricting harmful substances, but alcohol-induced damage allows toxins and inflammatory molecules to flood neural circuits, undermining memory and mood. The gut microbiome, shaped by diet and alcohol, communicates with the brain via metabolites and immune signals, playing a key role in BBB regulation. Yet, until now, causal evidence between alcohol, microbiome changes, BBB disruption, and cognition was missing.

The study enrolled 30 adult males with AUD and 30 healthy controls, measuring cognitive function with MMSE and MoCA, mood via anxiety and depression scales, sleep quality, and clinical chemistry related to liver function. Fecal DNA sequencing showed AUD subjects had depleted beneficial Faecalibacterium and increased harmful Streptococcus bacteria. Plasma metabolomics revealed altered lipid and amino acid profiles linked to these microbial changes but did not establish direct cognitive correlations.

To prove causation, researchers transplanted fecal microbiota from AUD patients or healthy donors into germ-free mice. AUD microbiota recipients showed increased BBB leakage in the prefrontal cortex and hippocampus, reduced tight junction proteins (ZO-1, occludin, claudin-5), and impaired memory in maze and object recognition tests. Supplementing ethanol-exposed mice with Faecalibacterium prausnitzii restored BBB integrity, boosted short-chain fatty acids (SCFAs), and improved cognitive performance.

These SCFAs help strengthen endothelial junctions, modulate inflammatory pathways, and support neurovascular health. Although the microbial community was altered rather than fully restored, supplementation of this next-generation probiotic presents a promising therapeutic avenue to protect against alcohol-related brain damage. Future work must clarify optimal dosing, sex-specific effects, and integration with lifestyle modifications.

This study highlights a critical gut-brain mechanism by which everyday alcohol use can silently raise neurovascular and cognitive risks and supports microbiome-targeted strategies for safeguarding brain health in AUD populations.

REFERENCE: Li, C., Wang, H., Lin, X., Zeng, G., Li, X., Chen, W., Lu, H., Pan, J., Zhang, X., Rong, X., He, L., & Peng, Y. (2025). Chronic alcohol consumption disrupts the integrity of the blood-brain barrier through the gut-brain axis. Commun Biol. DOI: 10.1038/s42003-025-09235-w. https://www.nature.com/articles/s42003-025-09235-w