The study conducted by Ashoka University and IISER, Manauli, Punjab
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Men and women differ in their susceptibility to infections, autoimmune diseases, and responses to vaccines. However, the underlying mechanisms are not fully understood. Recently, the microbiota — the diverse community of microorganisms residing in animals — has emerged as a potential contributor to sex-specific immune outcomes.
A recent study conducted by Ashoka University and IISER, Manauli, Punjab – titled ‘Exploring the role of microbiota in mediating sexually dimorphic infection outcomes in mealworm beetles’ – explored 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.
This, though, is not the first time a study examined the influence of microbiota composition on immunity. However, the authors say that there is limited direct evidence showing that microbiota differences cause differences in pathogen susceptibility. But Ashoka University, IISER, Manauli, researchers stumbled upon an interesting factoid while working with the beetle Tenebrio molitor. The researchers–Srijan Seal, Devashish Kumar, Pavankumar Thunga, Pawan Khangar, Manish Gupta, Dipendra Nath Basu, Rhitoban Roychoudhury and the team leader, Imroze Khan–have observed notable differences in microbiota composition between the sexes, along with a surprising finding: females were more susceptible to a bacterial infection than males. “This prompted us to investigate whether the observed susceptibility was linked to the microbiota and whether modifying it could influence infection outcomes,” the researchers say.
The question before the researchers was whether sex-specific differences in microbiota composition could be associated with differences in susceptibility to bacterial infection. “We also wanted to test whether altering the microbiota — by depleting it or reintroducing it — would change the degree of susceptibility in males and females,” the researchers say.
Sex, a key factor
The answer was ‘yes’. Immune responses and infection outcomes are not solely driven by genetic or hormonal factors, but can also be shaped by the microbiota. Environmental influences, such as diet and microbial exposure, have a key role in regulating immunity. By showing that the microbiota has a negative impact on infection resistance in females, but not in males, the researchers revealed 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,” they say.
The results revealed significant sex-specific effects. Under normal conditions, males were more successful at surviving infection, exhibiting lower bacterial loads and better infection clearance than females. When the microbiota was depleted, female survival significantly improved, effectively narrowing the gap between sexes. In contrast, male survival remained unchanged after microbiota depletion. Notably, when microbiota-depleted females were recolonised by consuming faecal matter, their susceptibility to infection returned to baseline levels. These findings suggest that the microbiota plays a detrimental role in female infection outcomes, while having little to no effect on males.
These findings suggest that the microbiota serves as a critical mediator of sex differences in human immune function, with implications for medicine, epidemiology, and public health. They challenge the view that immunity is governed solely by intrinsic genetic or physiological traits, highlighting the influence of microbial communities. The study opens new avenues for understanding the interplay between sex, microbiota, and immunity and emphasises the importance of considering sex as a biological variable in both experimental design and therapeutic development.
However, the study also raises intriguing evolutionary questions. Why do females maintain a microbiota that appears to reduce their infection resistance? Could certain microbes provide other physiological advantages — such as aiding in reproduction or nutrient absorption — that outweigh the costs to immune defense? “These possibilities warrant further investigation,” the researchers say.
Published on September 22, 2025
