Bowdoin Science Journal

Biology

Unlikely Weapon: Marburg Virus

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                  From the Tartar army catapulting bubonic plague victims to their enemies in the 14th century (Hale, n.d.) to the 2001 Anthrax attacks, bioterrorism has a long, but often understated, history. When thinking of terrorism, the general population generally focuses on the prospect of nuclear weapons. However, given the increasing issue of microbial resistance and rapid mutation of viruses, we must not ignore the potential of bioterrorism. In particular, Marburg Virus, a viral hemorrhagic fever closely related to Ebola, is one of the most promising potential biological weapons that should be further studied for prevention measures.

Background

                    Marburg Virus (MARV) was first discovered through simultaneous outbreaks of the virus in German and Yugoslavian laboratories in 1967, which is believed to have been caused by exposure to Ugandan African green monkeys. 31 people fell ill, and 7 deaths were recorded (Centers of Disease Control and Prevention, n.d.). Since the initial outbreak, there have been irregular outbreaks in Africa throughout the years, ranging from 1 to over 250 reported human cases (Centers of Disease Control and Prevention, n.d.).

                  MARV is categorized as a filovirus, which is the same virus classification as Ebola. MARV is a severe hemorrhagic fever, defined by its high mortality rate of up to 90% (Centers of Disease Control and Prevention, n.d.; Leroy et al., 2011). A MARV infection starts off with common symptoms such as a fever, nausea, headaches, and muscle pain, but quickly escalates to gastrointestinal problems (stomach pain and vomiting), respiratory problems (chest pains and coughing), neurological issues (delirium), and hemorrhagic manifestations (skin rashes, nosebleeds, and vomiting blood) (Leroy et al., 2011). Unfortunately, the severity of a MARV infection has made it a contender as a biological weapon.

Potential for Bioterrorism

                  MARV is often considered to be an effective agent of bioterrorism. According to the Centers for Disease Control and Prevention, MARV is a Category A (high-priority) pathogen based on the following criteria: a high transmission rate, high mortality rate and potential for major public health impact, potential for public panic, and requires special action for public health preparation (Centers for Disease Control and Prevention, 2024). MARV can also be aerosolized (turning infected body fluids or excrements into a fine mist) for higher transmission through the air, produced in large industrial quantities, and is spread from person to person (Filoviridae, n.d., Texas Department of State Health Services). In the Soviet Union’s Biological Weapons program, MARV was one of the strategic-operational weapons (meant for long-distance and short-distance targets) that would have been used in future wars (Tucker, 1999). The Soviet Union actually preferred MARV over Ebola because MARV’s weaponized form was more stable than Ebola’s (Filoviridae, n.d.). Considering MARV’s potential for bioterrorism, it is essential to develop prevention methods.

Vaccines in Development

                  While MARV is widely regarded as a high-priority pathogen with likely devastating consequences, there is still no known treatment or vaccine. However, within the last 5 years, two vaccine trials show great potential. One of the trials was tested on nonhuman primates, while the other trial was tested on humans. Both trials were successful in developing antibodies against MARV and didn’t have any severe side effects on the participants (O’donnell et al., 2023; Hamer et al., 2023).  These trials display promising results that can potentially mark a significant advancement in reducing the spread of MARV.

                  Initially only causing irregular outbreaks, MARV now has the potential to become a huge public health issue due to its potential for bioterrorism and high mortality rate. Therefore, the Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services awarded $21.8 million to the Sabin Vaccine Institute to continue developing a vaccine for MARV (Sabin Receives, 2022). Current vaccines in development show great potential to lessen MARV outbreak, though future studies need to continue monitoring the efficacy and safety of these vaccines. These measures highlight the importance of MARV vaccine research to protect global health from potential bioterrorism.

 

References

Centers of Disease Control and Prevention. (n.d.). About Marburg Virus Disease. Centers for Disease Control and Prevention. Retrieved July 15, 2023, from https://www.cdc.gov/vhf/marburg/about.html#:~:text=Marburg%20virus%20disease%20(MVD)%20is,within%20the%20virus%20family%20Filoviridae

Centers for Disease Control and Prevention. (n.d.). Marburg Virus Disease Outbreaks. Centers for Disease Control and Prevention. Retrieved July 15, 2023, from https://www.cdc.gov/vhf/marburg/outbreaks/chronology.html

Centers for Disease Control and Prevention. (2024, November 21). Emergency Preparedness and Response. Emergency Preparedness and Response. https://www.cdc.gov/emergency/index.html

Filoviridae. (n.d.). Federation of American Scientists. Retrieved December 7, 2024, from https://programs.fas.org/bio/factsheets/ebolamarburgfs.html

Hale, Kristina. (n.d.) Yersinia pestis as a Biological Weapon—Insects, Disease, and History | Montana State University. (n.d.). Retrieved December 7, 2024, from https://www.montana.edu/historybug/yersiniaessays/hale.html

Hamer, M. J., Houser, K. V., Hofstetter, A. R., Ortega-villa, A. M., Lee, C., Preston, A., Augustine, B., Andrews, C., Yamshchikov, G. V., Hickman, S., Schech, S., Hutter, J. N., Scott, P. T., Waterman, P. E., Amare, M. F., Kioko, V., Storme, C., Modjarrad, K., Mccauley, M. D., . . . Stanley, D. A. (2023). Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored marburg virus (cAd3-Marburg) vaccine in healthy adults in the usa: A first-in-human, phase 1, open-label, dose-escalation trial. The Lancet, 401(10373), 294-302. https://doi.org/10.1016/s0140-6736(22)02400-x

Leroy, E.m., Gonzalez, J.-P., & Baize, S. (2011). Ebola and marburg haemorrhagic fever viruses: Major scientific advances, but a relatively minor public health threat for africa. Clinical Microbiology and Infection, 17(7), 964-976. https://doi.org/10.1111/j.1469-0691.2011.03535.x

O’donnell, K. L., Feldmann, F., Kaza, B., Clancy, C. S., Hanley, P. W., Fletcher, P., & Marzi, A. (2023). Rapid protection of nonhuman primates against marburg virus disease using a single low-dose vsv-based vaccine. EBioMedicine, 89, 104463. https://doi.org/10.1016/j.ebiom.2023.104463

Sabin Receives Additional $21.8 Million From BARDA to Advance Marburg Vaccine. (2022, September 13). Sabin Vaccine Institute. Retrieved July 21, 2023, from https://www.sabin.org/resources/sabin-receives-additional-21-8-million-from-barda-to-advance-marburg-vaccine/

Texas Department of State Health Services. (n.d.). Viral Hemorrhagic Fevers and Bioterrorism.

Tucker, J. B. (1999). Biological weapons in the former Soviet Union: An interview with Dr. Kenneth Alibek. The Nonproliferation Review, 6(3), 1–10. https://doi.org/10.1080/10736709908436760

New Development of a Skin Probiotic to Combat Eczema

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The underlying factors contributing to the common condition of atopic dermatitis, more commonly referred to as eczema,  are generally related to an imbalance in the skin microbiome. The skin is home to an abundance of different species of bacteria, and most are symbiotic with humans and provide many defenses against invading pathogens. One of these symbiotic bacteria is called Roseomonas Mucosa (R. Mucosa), and it is this bacteria that has been found to be essential to maintaining a well-balanced and healthy skin microbiome, which in turn protects us from invaders such as Staphylococcus Aureus, the primary cause of eczema. Researchers from the National Institutes of Health were recently able to find genetically different versions of R. Mucosa that were better in their protective ability and were able to incorporate them into a skin probiotic cream that is effective in safely treating eczema.

  In their study, different strains of R. Mucosa, based on their differing metabolic profiles, were applied to eczema-affected patients, and the amount of recovery was quantified and compared. (Myles, et al.,2018) These differing metabolic profiles are important because they refer to the type and amount of certain lipids (fats) that are excreted by R. Mucosa that are essential in initiating a sequence in which the epithelial (skin) layer is repaired. (Myles, et al.,2020) In addition to comparing the different strains of R. Mucosa, researchers tested the responses to different environmental conditions to see how the possible treatment would be impacted by other topically applied solutions and the general presence of certain chemicals on the skin. Part of this was done by testing the growth of different strains of R. Mucosa, as well as S. Aureus, in the presence of different commonly marketed treatment lotions with known names. (Myles, et al.,2018)

               The study found that certain strains of R. Mucosa were more effective at reducing the impacts of eczema (NIAID, 2024)(Myles, et al.,2018) and the lipids produced by the effective strains were isolated and noted. The strains that produced the helpful lipids and a sufficient quantity of them were identified (Categorized as R. Mucosa HV). (Myles, et al.,2018) When the strains of R. Mucosa and S. Aureus were placed in differing environments, it was found that while most current market treatment products don’t inhibit the beneficial R. Mucosa growth, they may aid in the harmful eczema-causing bacteria S. Aureus. This suggested that these market products not be taken in conjunction with the new probiotic treatment. (Myles, et al.,2018)

  The study and subsequent clinical trial found that the transplantation of R. Mucosa onto an affected skin microbiome that is susceptible and/or subjected to eczema can lead to a reduction of the harmful effects related to eczema. It was tested further through clinical trials and has since been rolled out under the name Defensin, produced by Skinesa. Further studies are working to form an application to the FDA in order to roll out the probiotic cream as a regulated non-prescription drug so as to be more widely available to those who may benefit from it. (NIAID, 2024)

 

 

 References

(1) Myles, I. A., Castillo, C. R., Barbian, K. D., Kanakabandi, K., Virtaneva, K., Fitzmeyer, E., Paneru, M., Otaizo-Carrasquero, F., Myers, T. G., Markowitz, T. E., Moore, I. N., Liu, X., Ferrer, M., Sakamachi, Y., Garantziotis, S., Swamydas, M., Lionakis, M. S., Anderson, E. D., Earland, N. J., & Ganesan, S. (2020). Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. Science Translational Medicine, 12(560). https://doi.org/10.1126/scitranslmed.aaz8631

(2) Myles, I. A., Earland, N. J., Anderson, E. D., Moore, I. N., Kieh, M. D., Williams, K. W., Saleem, A., Fontecilla, N. M., Welch, P. A., Darnell, D. A., Barnhart, L. A., Sun, A. A., Uzel, G., & Datta, S. K. (2018). First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI Insight, 3(9). https://doi.org/10.1172/jci.insight.120608

(3) NIAID Discovery Leads to Novel Probiotic for Eczema. (2024, June 26). Nih.gov. https://www.niaid.nih.gov/news-events/niaid-discovery-leads-novel-probiotic-eczema?utm_medium=social&utm_source=linkedin&utm_campaign=news_probiotic_eczema_6262024

 

Asthma and ADHD: How do Pediatricians Approach This Intersection?

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According to the CDC, 11.4% of children aged 3-17 in the USA are diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) (Data and Statistics on ADHD | Attention-Deficit / Hyperactivity Disorder (ADHD), 2024). ADHD is a developmental disorder characterized by symptoms of hyperactivity, impulsivity, and inattention, as the name suggests. Treating this disorder often requires a variety of approaches including medication, psychotherapy, and workplace or school-based accommodations (Attention-Deficit/Hyperactivity Disorder – National Institute of Mental Health (NIMH), n.d.).  Comorbidities are very common in people with ADHD, this makes it so that it is rarely the only concern during a primary care visit (Silver, 2024). Sleath et al. discuss the communication primary physicians held with families with children that have both ADHD and asthma. There has been found to be a correlation between the severity of ADHD and asthma symptoms (Blackman & Gurka, 2007). In turn, balancing treatment for both primary care visits was a driver for the paper. Asthma is a chronic lung condition that results in the narrowing of the lung pathways. Medication to alleviate symptoms of both ADHD and asthma is often prescribed at primary care visits hence the study of their intersection. 

Figure 1. Happy little girl and pediatrician doing high five after medical checkup. AAP Schedule of Well-Child Care Visits. (2023). Healthy Children.org. https://www.healthychildren.org/English/family-life/health-management/Pages/Well-Child-Care-A-Check-Up-for-Success.aspx

Sleath et al. approach this balance by studying the communication between patients with ADHD and asthma and pediatricians. The study focuses on the communication breakdown when the patient has ADHD during an asthma visit. All of these were pediatric visits. To measure the effectiveness of communication, the American Association of Pediatrics (AAP) guidelines for discussing ADHD were used. The percentage of adherence was measured through the visits using recordings. 

Before data collection eligibility tests were conducted. This made sure that all participants in the study were 8-16 years of age, could speak English, was capable of filling out an assent form, had had at least one prior visit to the clinic, had persistent asthma, and had a guardian present who is over the age of 18 and is competent in English. After the visits concluded, guardians were provided with questionnaires, and children were interviewed. These were used to supplement the recordings. 

The audio taping and coding are the backbone of the data. The audio tapes were transcribed by a coding tool that was flagged for AAP guidelines. To ensure accuracy two research assistants met twice a month to review and refine criteria. The other important aspect of the collection was a thorough socio-demographic data set: gender, age, race, insurance, and tears of asthma. All demographic data but asthma status was also recorded from guardians. 

The results yielded from this were extreme. Throughout the visits 23% of the 296 children had ADHD noted in their medical chart. It was found that boys were more likely to have ADHD diagnoses. It is important to note that it is not because ADHD affects males more, but women are less likely to get diagnosed or are diagnosed later in life due to inattentive presentations (Attoe & Climie, 2023). When understanding the extent of utilization of AAP guidelines, categories were formed; functioning, outcomes, treatment plan, ADHD asthma relationship, chronic and follow-up visits. In all of these categories, the percentage of providers that used AAP guidelines never rose above 40%. In the adherence to medication, only one provider out of the 35 discusses the topic (41 providers participated, but recording forms only 35 were usable). Overall, it was shown that AAP guidelines were more likely to be followed if the visit was unrelated to asthma, highlighting providers’ tendency to neglect proper ADHD management in patients with comorbidities. 

The aim was to highlight the need for better communication practices in the pediatric setting. Particularly in cases where comorbid conditions are present. Future development in this field would be understanding the reason behind the present communication pattern. Approaching the issue from the physician and patient perspective. On the other hand, research on how to remedy the disparity in guideline adherence. 

 

Article based on ‘Communication about ADHD and its treatment during pediatric asthma visits’

Sleath, B., Sulzer, S. H., Carpenter, D. M., Slota, C., Gillette, C., Sayner, R., Davis, S., & Sandler, A. (2014, Feb). Communication about ADHD and its treatment during pediatric asthma visits. Community Ment Health J ., 50(2), 185-192. 10.1007/s10597-013-9678-3

References

AAP Schedule of Well-Child Care Visits. (2023). Healthy Children.org. https://www.healthychildren.org/English/family-life/health-management/Pages/Well-Child-Care-A-Check-Up-for-Success.aspx

Attention-Deficit/Hyperactivity Disorder – National Institute of Mental Health (NIMH). (n.d.). National Institute of Mental Health. Retrieved November 1, 2024, from https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd

Attoe, D. E., & Climie, E. A. (2023, March 30). Miss. Diagnosis: A Systematic Review of ADHD in Adult Women. J Atten Disord, 27(7), 645–657. 10.1177/10870547231161533

Blackman, J. A., & Gurka, M. J. (2007). Developmental and Behavioral Comorbidities of Asthma in Children. Journal of Developmental & Behavioral Pediatrics, 28(2), 92-99. 10.1097/01.DBP.0000267557.80834.e

Data and Statistics on ADHD | Attention-Deficit / Hyperactivity Disorder (ADHD). (2024, May 22). CDC. Retrieved November 1, 2024, from https://www.cdc.gov/adhd/data/index.html

Silver, L. (2024, April 3). ADHD Symptoms Or ADHD Comorbidity? Diagnosing Related Conditions. ADDitude. Retrieved November 1, 2024, from https://www.additudemag.com/when-its-not-just-adhd/

Sleath, B., Sulzer, S. H., Carpenter, D. M., Slota, C., Gillette, C., Sayner, R., Davis, S., & Sandler, A. (2014, Feb). Communication about ADHD and its treatment during pediatric asthma visits. Community Ment Health J ., 50(2), 185-192. 10.1007/s10597-013-9678-3

Sunshine, Sea, and Sunscreen: How ‘Eco-Friendly’ Choices Affect Marine Life

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Since the onset of the COVID-19 pandemic in 2020, international tourism has slowly been returning to previous levels. As of July 2024, an estimated 790 million tourists have traveled internationally, marking an 11% increase from the prior year and approaching the frequency of pre-COVID travel (Global Tourism Statistics). While this rise sounds promising for economic stimulation and cultural preservation, it also reintroduces the environmental impacts associated with tourism. In the Mediterranean, for example, tourists seeking to enjoy sunny beach days may unknowingly disrupt local ecosystems through their sunscreen use. Knowing how our consumption and product use impacts environmental systems is a key factor in being able to pinpoint where environmental degradation is coming from, and being able to stop it at the source. This raises the question: do “eco-friendly” sunscreens truly provide a safer alternative?

Pedro Echeveste, a researcher in marine microbial ecology and ecotoxicology at the University of the Balearic Islands, and his team have investigated this topic. Their 2024 study focused on commercial sunscreens and their chemical components’s impact on bacterial communities linked to Posidonia oceanica, or Neptune grass, a foundational species in the Mediterranean ecosystem (Echeveste et al., 2024).

Figure 1. Overview of all experimental results. The image shows all the different types of bacteria and epiphytes tested, and how their cell abundance shifted based on the type of sunscreen added to their system (Echeveste et al., 2024).

The study examined both heterotrophic bacteria (including Pseudomonas azotifigens, Marinobacterium litorale, Thiothrix nivea, Sedimentiacola thiotaurini, and Cobetia sp.) and autotrophic bacteria (Halothece sp. and Fischerella muscicola), as well as epiphytes—plants growing on the leaves of Neptune grass without being parasitic. These bacterial communities were cultured in artificial seawater at 25°C, with a 12-hour light/dark cycle and an initial concentration of 10^5 bacteria per mL. The research team added various concentrations of nanoparticles and sunscreens (0, 0.01, 0.1, 1, 10, and 100 mg/L) to each sample, exposing the bacterial communities for 72 hours.

Two commonly used inorganic UV filters, titanium dioxide (TiO₂) and zinc oxide (ZnO), were tested due to their prevalence in commercial sunscreens. The study focused on three sunscreen types: an eco-friendly SPF 50 without nanoparticles (SPF50E), an SPF 50 containing TiO₂ nanoparticles (SPF50), and an SPF 90 with both TiO₂ and ZnO nanoparticles (SPF90).

After the 72-hour exposure, the pollution concentrations that led to a 10% population decline (known as the EC10 value) were recorded. Titanium dioxide proved toxic to all heterotrophic bacteria, with Thiothrix nivea exhibiting a 10% decline at a concentration of 3.8 mg/L. Zinc oxide was comparatively less harmful, affecting only Marinobacterium litorale and Pseudomonas azotifigens at an EC10 of 1.39 mg/L for the latter.

The effects varied among the sunscreen types. The eco-friendly SPF 50 reduced phosphorus uptake by 30-50% in most bacterial species, a significant alteration that suggests interference with key nutrient cycles. The regular SPF 50, containing TiO₂, decreased alkaline phosphatase (APA) activity, an enzyme necessary for cell communication via dephosphorylation. Dephosphorylation—the removal of a phosphate group—is a critical process for signal transmission within cells. All sunscreens in the study also led to increased levels of reactive oxygen species (ROS), molecules derived from oxygen that may damage cellular proteins, DNA, and other essential structures. This data allows us to assume that any form of sunscreen, no matter the label as “eco-friendly”, or the SPF value, can impose degradational effects on our environmental systems via one mode or another.

All in all, These findings reveal that eco-friendly labels sometimes lack scientific backing, failing to account for subtle but important factors in maintaining environmental balance. Even the “eco-friendly” SPF 50 sunscreen altered bacterial populations, calling into question the validity of eco-friendly claims. 

As tourism resumes in coastal areas, the increased use of sunscreens—and thus UV filters—places greater pressure on marine ecosystems (Raffa et al., 2018). This rise in sunscreen pollution underscores the importance of studying the effects of “eco-friendly” sunscreens, as even minor shifts in bacterial populations can compound into substantial ecosystem changes when multiplied by millions of beachgoers. Achieving a truly eco-friendly sunscreen remains a challenge, but as consumers, what we can do is adopt a more informed and thoughtful approach to product choices. By balancing our personal protection needs with the planet’s health, we can work toward solutions that better align with environmental preservation.

 

References:

  1. Un tourism: Bringing the world closer. UN Tourism World Tourism Barometer | Global Tourism Statistics. Available at: https://www.unwto.org/un-tourism-world-tourism-barometer-data#:~:text=International%20tourist%20arrivals%20hit%2096,4%25%20less%20than%20in%202019 (Accessed: 28 October 2024). 
  2. Echeveste, P., Fernández-Juárez, V., Brito-Echeverría, J., Rodríguez-Romero, A., Tovar-Sánchez, A., & Agawin, N. S. (2024). Toxicity of inorganic nanoparticles and commercial sunscreens on marine bacteria. Chemosphere, 364, 143066. https://doi.org/10.1016/j.chemosphere.2024.143066
  3. Raffa, R.B. et al. (2018) Sunscreen bans: Coral reefs and skin cancer, Wiley Journal of Clinal Pharmacy and Therapeutics. Available at: https://research.ebsco.com/c/ceyvtd/viewer/pdf/db53bg7blv (Accessed: 28 October 2024).

 

Gut Viruses Might Be the Key to Life Saving Early Pancreatic Cancer Diagnosis

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New study links the community of viruses in our gut to early pancreatic cancer development – a potentially lifesaving discovery.

With a mortality-to-incidence ratio of over 90%, pancreatic cancer (PC) is among the most deadly forms of cancer. Since its early stages often bear no distinct symptoms, the disease grows stealthily until it’s too late. What’s more? Scientists foresee a near 100% increase in PC deaths, from 466 000 in 2020 to over 800 000 by 2040. To avert this grim future, researchers strive to develop methods for earlier detection, and subsequent earlier treatment. A 2022 study at the University of Tokyo linked PC to changes in gut microbiome composition. This has directed gastroenterologists’ focus to the microbiome in the search for new diagnostic tools.

The gut microbiome is often understood as the community of bacteria living in symbiosis with our digestive tract. Bacteria, like E. coli, break down our food in exchange for a safe habitat. However, bacteria do not aid our digestion for brownie points. As evolving creatures, they constantly test the limits of our gut ecosystems. As far as we understand, that’s where viruses come in; they regulate the bacterial population in our guts. The microbiome, therefore, consists of not only bacteria but also viruses. All viruses together make up our body’s virome.

An imbalance of bacteria and viruses has previously been observed in PC patients and is believed to be a factor in PC development. For example, the bacterium Roseburia intestinalis is significantly less abundant in the guts of PC patients compared to healthy individuals. This particular bacterium produces a cancer-inhibiting metabolite called butyrate, a substance that limits cancer development by suppressing inflammation and reducing the expression of genes involved in tumor cell growth. Other bacteria produce cancer promoting-metabolites, like lipopolysaccharide (LPS). This substance activates our immune system in the presence of pathogens, but also stimulates inflammation, and therefore, promotes cancer growth in the process. The balance of bacteria producing these two kinds of metabolites depends on the virome’s composition. Therefore, if we could identify the gut viruses causing imbalances, we might be able to diagnose patients earlier.

Researchers at Xi’an Jiaotong University took on this hypothesis when they performed a study that compared PC patient viromes to those of healthy individuals. They sequenced the DNA of 183 fecal samples from a Spanish and a German cohort with 101 PC patients and 82 healthy individuals. After sequencing the samples, they filtered out human DNA by comparing the sequenced DNA to an established human reference genome. They then used viral references to compare viral DNA from the samples to known viruses. After statistical analyses confirmed significant difference between the PC patient group and the healthy group, they identified which viruses were present in the PC patients’ guts, and how those differed from the ones found in healthy individuals. As pancreatic cancer severity increased, virome diversity decreased in PC patients. Additionally, the viruses present in the affected individuals targeted different bacteria compared to the gut viruses found in healthy individuals, offering a potential explanation for the relationship between unbalanced microbiomes and cancer growth.

Using their results, the researchers created models to differentiate PC patients from healthy individuals. These models succeeded with 87.9% accuracy. Though these findings do not offer the ultimate solution to late PC diagnoses, access to virome information could be used as a diagnostic tool in addition to the tools currently available. Namely, a viral DNA sequencing-based tool could identify the specific viral biomarkers linked to pancreatic cancer. In the future, at risk groups for PC might, therefore, be asked to supply fecal samples for gut virus analysis during routine check-ups. In the case that PC-linked biomarkers show up, these at-risk groups could be provided early treatment, potentially saving their lives.

Sources:

Miyabayashi, K., Ijichi, H., & Fujishiro, M. (2022). The Role of the Microbiome in Pancreatic Cancer. Cancers, 14(18), 4479. https://doi.org/10.3390/cancers14184479  

Zhang, P., Shi, H., Guo, R., Li, L., Guo, X., Yang, H., Chang, D., Cheng, Y., Zhao, G., Li, S., Zhong, Q., Zhang, H., Zhao, P., Fu, C., Song, Y., Yang, L., Wang, Y., Zhang, Y., Jiang, J., & Wang, T. (2024). Metagenomic analysis reveals altered gut virome and diagnostic potential in pancreatic cancer. Journal of Medical Virology, 96(7). https://doi.org/10.1002/jmv.29809

Cover image by magicmine, https://stock.adobe.com/search?k=pancreas+cancer&asset_id=343535067

An Overview of Alzhimer’s Disease Pathogenesis

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Keywords: pathogenesis, cholinergic changes, oxidative stress, amyloid plaque, Tau protein, mutation

Introduction

As people get older, many health complications begin to arise, many of which are cognitive. One such health complication is Alzheimer’s Disease (AD), which is one of the most common cause of dementia. AD is a disease that impacts fifty-five million people worldwide and one in three people over the age of eighty five experience advanced symptoms and signs of AD (Twarowski and Herbet 2023). AD is incurable and often leads to death, and currently a lot about how this disease works and about how it can be treated is unknown. AD is a complex multifactorial disease, and scientist are looking at many different causes (Twarowski and Herbet 2023). I will be covering the current understanding of AD pathogenesis (the process by which a disease is formed) through multiple lenses and discuss current treatments for AD. 

AD Pathogenesis Overview 

Cholinergic changes: 

One of the major neurotransmitters that allows for muscle movement, regulating heartbeat and blood pressure, and certain brain functions, is acetylcholine. Acetylcholine is active in the cerebral cortex, the basal ganglia, and the forebrain, and one of the first hypotheses for AD was cholinergic changes (Twarowski and Herbet 2023). A cholinergic change refers to the changes in the cholinergic system which is a neurotransmitter (acetylcholine) system that plays a role in memory, digestion, control of heartbeat, and movement (Sam and Bordoni 2023). When the nucleus basalis degenerates, there is a loss of synaptic connections that result in the deficiency of neurotransmission  (Twarowski and Herbet 2023). This can thus impact memory and movement, which are some of the most common symptoms of AD. The initial stages of AD are related to cholinergic changes and as the disease progresses, the cholinergic system loses its function until it all function is lost, resulting in death  (Twarowski and Herbet 2023).  

Figure 1. Demonstration of the cholinergic system in a neuron (Hall 2020 Mar 13).

Amyloid plaques and Tau proteins:

Amyloid plaques and the malfunction of Tau proteins are suspected to be two of the causes of AD that both lead to disease progression. Beta amyloids are small water-soluble peptides, and plaques will form if the beta amyloids do not have a stable structure (Twarowski and Herbet 2023). This lack of structure is thought of to be a cause of mutations. These plaques exhibit toxic properties to neuronal cells which causes neurons to degenerate (Twarowski and Herbet 2023). A Tau protein is a protein that promotes the assembly of tubulin which is a protein that is involved in cell division and cell movement. A Tau protein that is not functioning due to neurotoxins will bind to other Tau proteins and create tangles inside a neuron that lead to apoptosis of the neuron (Twarowski and Herbet 2023). This accumulation of plaques can cause the Tau proteins to form together and lead to tangles, revealing how there is a link between the two cause of AD (What Happens to the Brain in Alzheimer’s Disease? 2024 Jan 19). This process usually occurs in the final stages of AD pathogenesis.  

Figure 2. Amyloid beta plaques and Tau protein tangles impact on Neuron (McLoughlin).

 

Oxidative Stress: 

Another cause of AD is increased oxidative stress, which has many implications on people with AD. Oxygen is particularly important to the brain as the brain uses around twenty percent more oxygen than other organs in the body (Twarowski and Herbet 2023). Changes related to oxidative stress, which is an imbalance of free radicals and antioxidants in the body that leads to cell damage, are often seen in people with AD. This damage is caused by lipid oxidation as a result of oxidative stress breaks bonds in DNA molecules which increases the aging and death of neurons. These changes can also influence the mutation of Tau protein into advanced glycoxidation end products (AGEs) which are toxic to neurons and also lead to the progression of AD (Twarowski and Herbet 2023).  

Figure 3. Cell undergoing oxidative stress (Moore 2022 May 17).

Mutations:

One of the main and most significant factors that is related to the pathogenesis of AD and ties all of the previous factors together is genetic mutations as mutations are related to both cholinergic changes and oxidative stress. However, mutations in the genes that encode for the amyloid precursor protein have been identified as the most dangerous genetic risk factor associated with the development of AD (Twarowski and Herbet 2023). These are mutations in the 34 allele which is the allele of apolipoprotein E have been found to occur within one and five Alzheimer’s patients, and the risk of developing AD increases threefold with this mutation. Furthermore, this mutation may lead to the amyloid beta plaques and thus cause AD (Twarowski and Herbet 2023). Mutations are thus the largest contributing cause to AD because they can have so many implications that lead to the pathogenesis of AD. 

Figure 4. DNA that has undergone a mutation (Scoville 2019).

Conclusion

AD is a disease that impacts many people and causes many deaths annually, so being able to find a cure is incredibly important. AD pathogenesis is extremely complex, and as of today, scientists do not fully understand its pathogenesis, but we are getting closer. Understanding how the processes that lead to AD pathogenesis is the first step to being able to help find treatments that will help millions of people. Thus, scientists are still working diligently to understand how this disease works and how our current understanding can be improved. 

 

 

Literature Cited

Hall A. 2020 Mar 13. ChAT in 3D: Understanding the central cholinergic system. LifeCanvas Technologies. https://lifecanvastech.com/whole-brain-imaging-of-the-central-cholinergic-system-through-immunolabeling-chat/.

McLoughlin L. A Guide To Tau Proteins & Tauopathies. Assay Genie. https://www.assaygenie.com/blog/protein-tau-and-tauopathies.

Moore M. 2022 May 17. Effects of Oxidative stress | HHC. Life Science product | Helvetica Health Care. https://www.h-h-c.com/what-is-oxidative-stress-and-how-does-it-affect-your-health/.

Sam C, Bordoni B. 2023. Physiology, Acetylcholine. PubMed. https://www.ncbi.nlm.nih.gov/books/NBK557825/.

Scoville H. 2019. 4 Types of DNA Mutations and Examples. ThoughtCo. https://www.thoughtco.com/dna-mutations-1224595.

Twarowski B, Herbet M. 2023. Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review. International Journal of Molecular Sciences. 24(7):6518. doi:https://doi.org/10.3390/ijms24076518.

What Happens to the Brain in Alzheimer’s Disease? 2024 Jan 19. National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease.

 

From Milk to Malignancy – Breast Cancer and its Metabolic Implications 

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The annual rise of cancer cases has created a high demand for new innovative treatments and has made cancer a prominent topic in the scientific community. According to the American Cancer Society (ACS), approximately 20 million new cancer cases were diagnosed worldwide in 2022, leading to 9.7 million deaths [1]. It is expected that by 2050, cancer cases will reach 35 million, largely due to population growth [1]. While significant advancements have been made in cancer research, the complexity of different cancer types presents challenges. 

One of the most prevalent forms is breast cancer, which, in 2022, was the second most common cancer in the U.S., with 2.3 million new cases, predominantly affecting women [2]. Unlike many cancers, breast cancer is not a single disease but a collection of subtypes characterized by distinct clinical, morphological, and molecular features. This heterogeneity makes it challenging to study and treat effectively. A recent study published in Nature Metabolism explores the metabolic differences between normal mammary cells and breast cancer cells [4]. Understanding these metabolic processes could pave the way for new, targeted therapies. Researchers have identified specific metabolic vulnerabilities in mammary epithelial cells, which line the breast tissue.

 

Figure 1. Non-tumorigenic Mammary Gland Components. A diagram of a non-tumorigenic mammary gland showing a cluster of alveoli containing luminal and basal cells. Luminal cells line the milk ducts and alveoli and are responsible for milk secretion during lactation. Basal cells are believed to play a role in transporting milk to the nipple during lactation. Source: Created in BioRender, [4], [10], [11].

In the normal mammary gland, various types of cells carry out specific functions, one of which is the progenitor cells. These progenitor cells generate distinct alveolar structures that continuously form in the adult breast, and their activity is crucial for maintaining normal mammary homeostasis [5]. Progenitor cells are located in the luminal compartment [6], which is also home to the luminal cells. The luminal cells play a key role in lactation by lining the milk ducts and alveoli, where they secrete milk (Figure 1)[7]. In contrast, basal cells are located around the luminal cells and are believed to function during lactation by helping to transport milk to the nipple (Figure 1)[7]. Although these mammalian epithelial cells (luminal and basal cells) are important to the function of normal mammary glands, these also serve as a tumour cell of origin [4].

In their study, Mahendralingam et al. used mass spectrometry to analyze the metabolic profiles of normal human mammary cells [8]. They discovered that luminal progenitor cells primarily rely on oxidative phosphorylation for energy, whereas basal cells depend more on glycolysis [4]. This distinction is crucial because oxidative phosphorylation is an efficient, oxygen-dependent process that generates substantial energy, while glycolysis, though faster, is less efficient and does not require oxygen — a pathway often favored by cancer cells to support rapid growth [9]. Targeting these distinct energy pathways could lead to more effective treatments for different breast cancer subtypes.

However, a new discovery was that breast cancer cells appear to adopt the metabolic programs of their cells of origin [4,9]. This complicates treatment since the cancer cells may still be vulnerable to metabolic pathways that are important for normal cell function. As a result, treatments designed to target specific metabolic pathways might not work as expected, since the cancer cells might behave similarly to the healthy cells from which they originated. 

The results from Mahendralingam et al. can form a basis for future metabolic studies that may lead to specific anti-tumoral drug therapies designed to treat specific breast cancer subtypes. This type of research lays a foundation for targeted approaches but further studies are needed to assess how findings, such as this one, can translate into clinical practice. As breast cancer continues to rise, understanding the complexity is more important than ever. 

 

Work Cited: 

  1. Global Cancer Facts & Figures. (n.d.). Retrieved October 27, 2024, from https://www.cancer.org/research/cancer-facts-statistics/global-cancer-facts-and-figures.html
  2. Global cancer burden growing, amidst mounting need for services. (n.d.). Retrieved October 27, 2024, from https://www.who.int/news/item/01-02-2024-global-cancer-burden-growing–amidst-mounting-need-for-services
  3. Sánchez López de Nava, A., & Raja, A. (2024). Physiology, Metabolism. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK546690/
  4. Alfonso-Pérez, T., Baonza, G., & Martin-Belmonte, F. (2021). Breast cancer has a new metabolic Achilles’ heel. Nature Metabolism, 3(5), 590–592. https://doi.org/10.1038/s42255-021-00394-8
  5. Tharmapalan, P., Mahendralingam, M., Berman, H. K., & Khokha, R. (2019). Mammary stem cells and progenitors: Targeting the roots of breast cancer for prevention. The EMBO Journal, 38(14), e100852. https://doi.org/10.15252/embj.2018100852
  6. Tornillo, G., & Smalley, M. J. (2015). ERrrr…Where are the Progenitors? Hormone Receptors and Mammary Cell Heterogeneity. Journal of Mammary Gland Biology and Neoplasia, 20(1–2), 63–73. https://doi.org/10.1007/s10911-015-9336-1
  7. New Paradigm for Mammary Glands. (n.d.). Massachusetts General Hospital. Retrieved December 8, 2024, from https://www.massgeneral.org/cancer-center/clinician-resources/advances/new-paradigm-for-mammary-glands
  8. Mahendralingam, M. J., Kim, H., McCloskey, C. W., Aliar, K., Casey, A. E., Tharmapalan, P., Pellacani, D., Ignatchenko, V., Garcia-Valero, M., Palomero, L., Sinha, A., Cruickshank, J., Shetty, R., Vellanki, R. N., Koritzinsky, M., Stambolic, V., Alam, M., Schimmer, A. D., Berman, H. K., … Khokha, R. (2021). Mammary epithelial cells have lineage-rooted metabolic identities. Nature Metabolism, 3(5), 665–681. https://doi.org/10.1038/s42255-021-00388-6
  9. ZHENG, J. (2012). Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncology Letters, 4(6), 1151–1157. https://doi.org/10.3892/ol.2012.928
  10. Fig. 3 Stem cell in glandular and stratified epithelia. A A schematic… (n.d.). ResearchGate. Retrieved December 7, 2024, from https://www.researchgate.net/figure/Stem-cell-in-glandular-and-stratified-epithelia-A-A-schematic-model-depicting-the_fig3_374804603
  11. Model of normal mammary gland structure. This tissue is composed of… (n.d.). ResearchGate. Retrieved December 8, 2024, from https://www.researchgate.net/figure/Model-of-normal-mammary-gland-structure-This-tissue-is-composed-of-ducts-which-are_fig1_357239665

Genomics of severe and treatment-resistant obsessive-compulsive disorder treated with deep brain stimulation: a preliminary investigation

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Obsessive-compulsive disorder (OCD) can be severely disabling, and some patients do not respond to standard treatments like medication and therapy. Deep brain stimulation (DBS), an invasive neurosurgical intervention where thin electrodes are connected to a neuro-pacemaker and introduced into subcortical central structures of the brain to modulate pathological neuronal activity with electrical current, has shown promise for these treatment-resistant cases. However, responses to DBS vary widely, prompting a need to identify genetic factors that might predict which patients will benefit. Understanding these genetic markers may ultimately lead to more personalized, effective approaches for treatment-resistant OCD.

This study (Chen et al, 2023) conducted a preliminary genomic analysis on a small cohort of patients with severe, treatment-resistant OCD who received DBS. Researchers sequenced the patients’ DNA to examine specific genetic variants. These included instances where a single nucleotide in a genomic sequence was altered in a phenomenon known as single nucleotide variants and among other genetic markers previously associated with psychiatric disorders and traits related to treatment resistance. Statistical analysis was then applied to explore any associations between these genetic markers and the clinical outcomes of DBS in these patients.

The results identified several genetic markers such as missense variants in the gene KNCB1 that seemed to correlate with positive or negative DBS responses. However, because the study involved a small number of participants, these findings are considered preliminary. Certain genetic variants showed potential as predictors for treatment outcomes, but further research with a larger sample size is needed to validate these associations and understand the mechanisms by which they influence DBS response.

This study provides initial evidence that genetics may play a role in how patients with treatment-resistant OCD respond to DBS. If validated by larger studies, these findings could pave the way for genetically-informed approaches to selecting and optimizing DBS candidates, contributing to more precise, personalized treatment strategies for severe OCD cases.

References:

Long Long Chen, Matilda Naesström, Matthew Halvorsen, Anders Fytagoridis, David Mataix-Cols, Christian Rück, James J Crowley, Diana Pascal (2023) Genomics of severe and treatment-resistant obsessive-compulsive disorder treated with deep brain stimulation: a preliminary investigation, medRxiv , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10153313/

Unveiling the Potential of PGCCs in Future Cancer Treatments

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Poly-ADP ribose polymerases (PARPs) are proteins that participate in the process of repairing single strand DNA breaks (SSBs). PARPs carry out surveillance in the cell and when DNA damage occurs, PARPs bind to and recognize DNA damage, setting off DNA repair pathways (Morales et al., 2014). PARP inhibitors (PARPi) block the DNA damage repair pathway, leaving the SSBs unrepaired. Eventually, the SSBs will accumulate and form double stranded breaks (DSBs).

Normal ovarian cells use BRCA proteins to recruit repair complexes to the DSB region and help repair the DSBs using a method called homologous recombination (HR) (Dilmac and Ozpolat, 2023). Homologous recombination is a process in which identical and undamaged nucleotide sequences from homologous chromosomes are used to repair DSBs. In BRCA-mutant ovarian cancer, DSBs are unable to be repaired because BRCA proteins lose function and are unable to recruit repair complexes.

While PARPi is a viable treatment for BRCA-mutant ovarian cancer, 40-50% of BRCA-mutant patients do not respond to PARPi due to innate or acquired PARPi resistance (Dilman and Ozoplat, 2023). Acquired resistance happens because cancer cells reproduce and adapt quickly to overcome the PARPi lethality. In addition, more than 50% of HGSC patients are do not have BRCA mutations, meaning that PARPi treatment are not substantially beneficial to a large majority of patients (Zhang et al., 2023). This highlights the importance of finding a different mechanism by which we can potentiate the therapeutic effect of PARPi treatment. The solution may lie in polyploid giant cancer cells (PGCCs).

Fluorescence light micrograph of a Polyploid giant cancer cell (PGCC) from a triple-negative breast cancer. The other cellular components highlighted here are actin (red), mitochondria (green), and nuclear DNA (blue).
Source: University Of Pittsburgh Cancer Institute. “Polyploid Giant Cancer Cell From Breast.” Photograph. Science Photo Gallery.

PGCCs are large cancer cells that are usually thought to be senescent, meaning that the cells age but do not die or divide. However, scientists are not entirely certain on the formation or function of PGCCs (Zhou et al., 2022).

In Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer, Zhang et al. investigates the association of PGCCs with the PARPi (specifically, Olaparib) resistance in ovarian cancer. Their research looks at high-grade serous carcinoma (HGSC), the most common subtype of ovarian cancer. First, they found that PGCCs grow in Olaparib-resistant HGSC patient-derived xenografts (PDX) and that they were able to induce PGCC formation using Olaparib. PDX is a model of cancer where cancer tissues are collected from patients and planted into an immunodeficient mouse. Second, while PGCCs are usually thought to be senescent, they found that PGCCs are also able to escape senescence and produce daughter cells that are able to divide. A portion of these mitotic competent daughter cells also have therapeutic resistance, increasing PARPi resistance within the tumor. So far, Zhang et al. found that not only can PGCCs become resistant to PARPi treatment, but they can also produce more cancer cells that are also resistant to PARPi treatment. However, this isn’t all bad news.

From previous studies, we know that PGCCs dedifferentiate and mimic early embryonic development (Niu et al., 2017). Leveraging this knowledge, Zhang et al. reasoned that certain contraceptives, such as Mifepristone, may be able to block the life cycle of PGCCs. Indeed, they found that Mifepristone was able to suppress tumor growth in both Olaparib-naive and Olaparib-resistant HGSC cells, treating the original issue of PGCC and daughter cells being resistant to Olaparib. The results showed that PGCCs are most sensitive to a combination of Olaparib and Mifepristone treatment. In conclusion, Zhang et al. found a way to grow PGCCs in HGSC cells and then use the PGCCs to suppress cancer growth while also overcoming PARPi resistance.

Zhang et al. mentioned that PGCCs can be used to potentiate the therapeutic response of PARPi treatment and combat more than one HGSC subtype. Previously, PARPi treatment worked best with BRCA mutant patients. However, Zhang et al. suggest that PGCCs, rather than the BRCA status of tumor, are associated with acquired Olaparib resistance. This means that PGCCs can be used as an alternative treatment regime, broadening applications of PARPi to HGSC patients who do not have BRCA mutations.

 

References:

Dilmac, S., & Ozpolat, B. (2023). Mechanisms of PARP-Inhibitor-Resistance in BRCA-Mutated Breast Cancer and New Therapeutic Approaches. Cancers, 15(14), 3642. https://di.org/10.3390/cancers15143642

Morales, J. C., Li, L., Fattah, F. J., Dong, Y., Bey, E. A., Patel, M., Gao, J., & Boothman, D. A. (2014). Review of Poly (ADP-ribose) Polymerase (PARP) Mechanisms of Action and Rationale for Targeting in Cancer and Other Diseases. Critical Reviews in Eukaryotic Gene Expression, 24(1), 15–28.

Niu, N., Mercado-Uribe, I., & Liu, J. (2017). Dedifferentiation into blastomere-like cancer stem cells via formation of polyploid giant cancer cells. Oncogene, 36(34), 4887–4900. https://doi.org/10.1038/onc.2017.72

Zhang, X., Yao, J., Li, X., Niu, N., Liu, Y., Hajek, R. A., Peng, G., Westin, S., Sood, A. K., & Liu, J. (2023). Targeting polyploid giant cancer cells potentiates a therapeutic response and overcomes resistance to PARP inhibitors in ovarian cancer. Science Advances, 9(29), eadf7195. https://doi.org/10.1126/sciadv.adf7195

Zhou, X., Zhou, M., Zheng, M., Tian, S., Yang, X., Ning, Y., Li, Y., & Zhang, S. (2022). Polyploid giant cancer cells and cancer progression. Frontiers in Cell and Developmental Biology, 10, 1017588. https://doi.org/10.3389/fcell.2022.1017588

The Dark Side of Antibiotics

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Antibiotics are medications that fight infections caused by bacteria. But they can also lead to mental health issues, such as anxiety and depression, later in life. 

The discovery of antibiotics was one of the greatest medical advances of the 20th century. Antibiotics have significantly reduced mortality from infectious diseases and increased average life expectancy. However, they have a variety of side effects, including cognitive impairment and emotional disorders in adulthood (Adedji 2016). 

Antibiotics destroy bacteria in the gut, which can disrupt brain function. Gut microbiota are an important component of the gut-brain axis–the two-way line of communication between the gastrointestinal tract and the central nervous system. Gut microbiota produce neurotransmitters that regulate mood, such as dopamine, norepinephrine, and serotonin, which travel through the vagus nerve to the brain (Karakan et al 2021). Previous studies have found that antibiotic-induced gut microbiota depletion causes dysfunction of the gut-brain axis, increasing anxiety and depression-related behaviors (Mosaferi et al 2021).

Aging plays an important role in the development of both gut microbiota and the brain. Microbiota first appear at birth and rapidly colonize the intestinal tract. The composition and diversity of gut microbiota resembles adult level by 2 years of age and remains stable throughout adulthood before decreasing in old age. The brain develops until the mid-to-late 20s and starts to decline in middle age. It has been shown that antibiotic-induced gut microbiota depletion has negative effects on the brain (Li et al 2022). However, no prior research has been done on this relationship during the different stages of life. This study aimed to determine the connection between gut microbiota and cognitive and emotional function during the different life stages. 

In this experiment, the researchers used mice as models for human subjects, randomly assigning 75 mice to five groups. One group served as the control (Veh group) and was given distilled water from birth to death. The other four groups were given an antibiotic cocktail at different life stages: birth to death (Abx group), birth to postnatal day 21 (Abx infant group), postnatal day 21 to 56 (Abx adolescence group), and postnatal day 57 to 84 (Abx adulthood group).  

At postnatal day 85, the researchers randomly selected thirteen mice from each group for testing. They measured the cognitive function and emotion of the mice by using four traditional behavioral tests: open-field test (OFT), passive avoidance test (PAT), morris water maze test (MWM), and tail suspension test (TST). The OFT measured anxiety level by observing how long the mice moved in an open field for 5 minutes. The PAT measured short-term memory, which was defined as the difference in latency–the time it took mice to reenter a room that delivered an electric shock–between day 1 and day 2 (Jahn-Eimermacher et al 2011). The MWM measured spatial memory, which was defined as incubation time, or how long it took mice to find a submerged platform in a pool after a 5-day training period. The TST measured depression state by observing the duration of quiescence (motionless state) of the mice while they were suspended upside down for 4 minutes.

Figure 1 | Results of OFT, PAT, MVM, and TST tests. Researchers conducted four traditional behavioral tests on mice given water, as well as mice given antibiotics at different stages of life: birth to death, infancy, adolescence, and adulthood. They found that exposure to antibiotics from birth to death and in infancy led to the most severe cognitive and emotional dysfunction, followed by exposure in adolescence and adulthood (Li et al 2022).

The results of this study suggested that life cycle stages influence the relationship between gut microbiota and cognitive and emotional function. For the OFT test, the total movement time of the Abx, Abx infant, and Abx adolescent groups was significantly lower than the Veh group, indicating they were more anxious than the Veh group (Figure 1). In other words, exposure to antibiotics from birth to death, in infancy, and in adolescence caused anxiety-related behaviors. For the PAT test, the difference in latency for every Abx group was significantly lower than the Veh group, meaning all Abx groups reentered the room with the electric shock more quickly after training. These results signaled that short-term memory loss was greater in the Abx groups than the Veh group; exposure to antibiotics at any stage of life caused short-term memory loss. The MWM test found that the incubation time after the 5-day training period was significantly higher for the Abx and Abx infant groups than the Veh group, so they experienced more spatial memory loss than the Veh group; exposure to antibiotics from birth to death and in infancy caused spatial memory loss. The TST test found that the duration of quiescence in the Abx and Abx infant groups was significantly higher than the Veh group, implying they were more depressed than the Veh group. In other words, exposure to antibiotics from birth to death and in infancy caused depression-related behaviors.

The researchers’ findings align with previous work showing that depletion of gut microbiota causes cognitive impairment and emotional problems (Lach et al 2020). Furthermore, the researchers demonstrated that life cycle stages are an important factor in the relationship between gut microbiota and cognitive and emotional function. In particular, their findings strengthened the idea that infancy is a crucial stage of development of gut microbiota and the brain (Hunter et al 2023). Gut microbiota lost in infancy recovers over time; however, this depletion has lasting cognitive effects. In this study, mice given antibiotics in infancy exhibited similar behaviors in adulthood as mice given antibiotics from birth to death: anxiety, depression, memory loss, and learning ability decline. Exposure to antibiotics in infancy and in the long term led to the most severe cognitive and emotional dysfunction, followed by exposure in adolescence and adulthood.

The researchers’ findings also have implications for the treatment of mental health illnesses. Previous studies have shown that probiotics replace depleted gut microbiota, alleviating symptoms of anxiety and depression. Antidepressants and anxiolytics–current medications for anxiety and depression–cause side effects such as nausea, weight gain, insomnia, constipation, dizziness, agitation, and restlessness. Probiotics are associated with milder side effects, including gas and bloating (Bistas et al 2023). Probiotics are unlikely to treat severe depression and anxiety, but they are promising treatments for people with milder conditions. The next step is to identify and manufacture effective probiotics, which would revolutionize the field of psychiatry and improve the lives of people around the world.

 

References

Adedji, W.A. 2016. THE TREASURE CALLED ANTIBIOTICS. Annals of Ibadan Postgraduate Medicine. 14(2):56-57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354621/.

Bistas KG, Tabet JP. 2023. The Benefits of Prebiotics and Probiotics on Mental Health. Cureus Journal of Medical Science. 15(8):e43217. doi:10.7759/cureus.43217.

Hunter S, Flaten E, Petersen C, Gervain J, Werker JF, Trainor LJ, Finlay BB. 2023. Babies, bugs and brains: How the early microbiome associates with infant brain and behavior development. PLOS One. 18(8):e0288689. doi:10.1371/journal.pone.0288689.

Jahn-Eimermacher A, Lasarzik I, Raber J. 2011. Statistical analysis of latency outcomes in behavioral experiments. Behavioural Brain Research. 221(1):271-275. doi:10.1016/j.bbr.2011.03.007.

Karakan T, Ozkul C, Akkol EK, Bilici S, Sobarzo-Sánchez E, Capasso R. 2021. Gut-Brain Microbiota Axis: Antibiotics and Functional Gastrointestinal Disorders. Nutrients. 13(2):389. doi:10.3390/nu13020389.

Lach G, Fülling C, Bastiaanssen TFS, Fouhy F, O’Donovan AN, Ventura-Silva AP, Stanton C, Dinan TG, Cryan JF. 2020. Translational Psychiatry. 10(1):382. doi:10.1038/s41398-020-01073-0.

Li J, Pu F, Peng C, Wang Y, Zhang Y, Wu S, Wang S, Shen X, Li Y, Cheng R, He F. 2022. Antibiotic cocktail-induced gut microbiota depletion in different stages could cause host cognitive impairment and emotional disorders in adulthood in different manners. Neurobiology of Disease. 170:105757. doi:10.1016/j.nbd.2022.105757.

Mosaferi B, Jand Y, Salari AA. 2021. Gut microbiota depletion from early adolescence alters anxiety and depression-related behaviors in male mice with Alzheimer-like disease. Scientific Reports. 11:22941. doi:10.1038/s41598-021-02231-0.