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Linking sex specific microbiota to variation in pathogen susceptibility

Research Summary: We showed that females had higher infection vulnerability, which decreased when microbiota was removed. Reintroducing microbiota restored this difference. This suggests that sex-specific immune responses in beetles may be shaped by microbiota.

Author interview

Srijan Seal
Srijan Seal

Srijan Seal completed his PhD in the year 2025 and is currently pursuing a post-doc at Utah State University. He is broadly interested in looking at host-pathogen and microbe-microbe interactions to answer fundamental questions in immunology like regulation of immune responses and how microbial interactions shape host immunity.

Twitter : @srijan_seal

Lab: Imroze Khan, Ashoka University

Website: https://evoecoimmunol.wordpress.com/author/imrozerkhan/

What was the core problem you aimed to solve with this research?

Sexual differences in immune responses are common across animal species and have significant implications for how diseases spread and how pathogens evolve. These sex-based differences can be influenced by various factors such as life history strategies and immune investment. Recently, the microbiota—the diverse community of microorganisms residing in animals—has emerged as a potential contributor to sex-specific immune outcomes. Our research aimed to explore whether differences in the microbiota between males and females could contribute to sexually dimorphic responses to infection, and whether manipulating the microbiota could alter those outcomes.

Linking sex specific microbiota to variation in pathogen susceptibility
Figure legend: Freshly eclosed adult beetles were assigned to one of three treatments: (A) a normal diet of regular wheat bran, (B) an antibiotic-supplemented diet, or (C) a microbiota-recolonization diet, where beetles were first fed antibiotics for six days followed by fecal supplementation. Females are generally more susceptible to infection than males and carry a higher bacterial load. Depletion of the microbiota increases female survival and reduces their bacterial load, while recolonization restores susceptibility. Males remain unaffected across all treatments.

How did you go about solving this problem?

We used Tenebrio molitor beetles as our model system and subjected them to different dietary treatments to manipulate their microbiota. One group was fed a standard diet (maintaining natural microbiota), another received a diet supplemented with broad-spectrum antibiotics to reduce the microbiota, and a third group involved females from the antibiotic-treated group that were fed fecal matter from other beetles to reintroduce microbial communities. Following these treatments, we infected all groups with the bacterial pathogen Bacillus thuringiensis and measured survival rates. We also assessed bacterial loads in the beetles, analyzed microbiota composition, and measured expression levels of immune genes, specifically two antimicrobial peptides—tenecin 1 and tenecin 2.

How would you explain your research outcomes (Key findings) to the non-scientific community?

Our results showed that males were generally better at clearing bacterial infections than females and had higher survival rates under normal conditions. When the microbiota was depleted using antibiotics, only females showed improved survival; male survival remained unchanged. This suggests that the microbiota negatively affected females’ ability to survive infection, while having no impact on males. When we reintroduced the microbiota into females through fecal feeding, their survival dropped again to levels seen under normal conditions, restoring the difference between the sexes. Interestingly, the recolonized females did not exactly regain their original microbiota composition, indicating that the specific microbial community structure may shift after manipulation.

What are the potential implications of your findings for the field and society?

Our study highlights that immune responses and infection outcomes are not solely driven by genetic or hormonal factors but can also be shaped by the microbiota. This emphasizes the role of environmental influences, such as diet and microbial exposure, in regulating immunity. By showing that the microbiota has a negative impact on infection resistance in females but not in males, we reveal that the immune–microbiota relationship may be fundamentally different between the sexes. This research contributes to a broader understanding of host–microbe interactions and suggests that sex should be considered a key factor in studies of immunity, disease susceptibility, and even in the design of microbiota-targeted therapies.

What was the exciting moment during your research?

One of the most exciting moments was when we discovered that females experienced higher mortality due to the presence of their inherent microbiota, in contrast to males. This was particularly surprising because most existing research suggests that the microbiota typically benefits the host by supporting immune function and overall health. Our findings challenged this assumption, indicating that in females, the microbiota may actually increase susceptibility to infection. This unexpected result raised new questions about the sex-specific roles of microbiota. While it’s possible that the female microbiota plays important roles in other physiological processes—such as digestion, nutrient absorption, or reproduction—its apparent negative impact on infection survival is both intriguing and significant. This opens up a fascinating avenue for further research into the complex and potentially conflicting functions of host-associated microbes across sexes.

Paper reference: Seal Srijan, Kumar Devashish, Thunga Pavankumar, Khangar Pawan, Gupta Manisha, Basu Dipendra Nath, Raychoudhury Rhitoban and Khan Imroze 2025. Exploring the role of microbiota in mediating sexually dimorphic infection outcomes in mealworm beetles. Biol. Lett.2120250136

http://doi.org/10.1098/rsbl.2025.0136


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