Megasphaera represents a genus of bacteria that plays various roles across different biological environments. These microbes are characterized by their strict anaerobic nature, meaning they thrive in conditions devoid of oxygen.
Defining Megasphaera
Megasphaera species are classified as Gram-negative bacteria, although they belong to the phylum Firmicutes (also known as Bacillota), which typically includes Gram-positive organisms. This atypical Gram-negative staining is attributed to a unique porous pseudo-outer membrane. These bacteria are strictly anaerobic, meaning oxygen is toxic to them, and they cannot grow in its presence.
Morphologically, Megasphaera are coccus-shaped, appearing as large, spherical cells, which is reflected in their name (“mega” for large and “sphaera” for sphere). Individual cells can range from 0.4 to 2.0 micrometers or more in diameter. They are non-motile and do not form spores.
Metabolically, Megasphaera are chemoorganotrophs, obtaining energy by fermenting various carbohydrates. They are known for their ability to break down sugars like glucose, fructose, and lactate. This fermentation process yields short-chain fatty acids (SCFAs), including acetate, propionate, butyrate, valerate, formate, and caproate. Notably, Megasphaera elsdenii, a prominent species, can uniquely utilize both D- and L-lactate isomers, which is important in specific environments.
Where Megasphaera Resides
Megasphaera species are found in various oxygen-deprived ecological niches across different hosts. They are commonly found within the mammalian gastrointestinal tract. This includes a significant presence in the rumen of ruminant animals such as cattle, sheep, and goats, where they are part of the dense microbial community.
In humans, Megasphaera resides in the large intestine. Beyond the gut, these bacteria inhabit the human urogenital tract, including the vagina, where they are considered part of the normal microbiota. Additionally, Megasphaera can be found in the oral cavity, contributing to the microbial communities of the tongue dorsum, tonsils, and saliva. Other habitats include spoiled beer and human clinical specimens like liver abscesses.
Impact and Applications of Megasphaera
Megasphaera species exert various influences in their respective habitats, contributing to both host health and sometimes disease. In ruminant animals, Megasphaera elsdenii plays a significant role in rumen function, primarily by consuming lactic acid. This bacterium converts lactate (a product of rapid sugar fermentation) into volatile fatty acids, mainly propionate, which stabilizes rumen pH and mitigates ruminal acidosis in animals fed high-grain diets. For this reason, M. elsdenii has been explored as a probiotic to promote rumen health and improve feed efficiency in livestock, potentially enhancing animal performance. However, M. elsdenii has also been associated with milk fat depression in dairy cows, though a direct causative link remains under investigation.
In the human gut, Megasphaera contributes to the production of short-chain fatty acids (SCFAs) such as butyrate, acetate, formate, and valerate. These SCFAs are important metabolites that regulate immune responses and maintain the integrity of the gut barrier. Lower Megasphaera abundance in the stool microbiota is associated with diarrheal symptoms during Cryptosporidium infections, indicating its potential involvement in shaping the gut microenvironment and influencing infection severity. Despite these benefits, Megasphaera elsdenii may increase gas production during in vitro fermentation by human fecal microbiota.
In the female urogenital tract, Megasphaera phylotypes are associated with bacterial vaginosis (BV), an imbalance in the vaginal microbiota. For example, phylotype 1 (MP1) is linked to BV and preterm birth, while phylotype 2 (MP2) is associated with trichomoniasis. These associations underscore the genus’s potential involvement in cervicovaginal infections and disease.
In the oral cavity, Megasphaera abundance increases in smokers. It has also been associated with dysbiotic conditions like periodontitis and certain cancers, including HPV-positive head and neck squamous carcinoma and lung cancer. Some species’ ability to produce various carboxylic acids offers potential for industrial applications.

