The gut microbiome, residing in the gastrointestinal tract, profoundly influences human health, metabolism, and immunity. Among the thousands of bacterial species inhabiting the gut, the genus Megasphaera has drawn scientific attention due to its unique metabolic capabilities and observed associations with various health states.
Classification and Habitat of Megasphaera
Megasphaera is a genus of Gram-negative, obligately anaerobic cocci, meaning it cannot survive in the presence of oxygen. Despite the Gram-negative staining, it belongs to the phylum Firmicutes, specifically within the class Negativicutes. This unusual classification is due to a distinct, porous cell wall structure.
The primary natural environment for this bacterium in humans is the lower gastrointestinal tract, specifically the colon. Researchers often use numerical identifiers like “Megasphaera 2” to refer to specific operational taxonomic units (OTUs) or distinct phylotypes identified in sequencing studies. These designations are a shorthand for particular genetic strains that are consistently observed in human samples, allowing researchers to track their precise roles and prevalence.
The Role of Megasphaera in Metabolic Processes
The central metabolic function of Megasphaera in the gut is its ability to utilize lactate, a compound that is a byproduct of other gut bacteria. Many beneficial microbes, such as Bifidobacterium species, ferment dietary carbohydrates into lactate, which can accumulate and lower the gut pH. Megasphaera species act as metabolic scavengers, consuming this excess lactate to maintain a balanced intestinal environment.
By consuming lactate, Megasphaera converts it into beneficial short-chain fatty acids (SCFAs), which are vital for host health. This process is an example of microbial cross-feeding, where the waste product of one bacterium becomes the food source for another. The specific SCFA produced depends on the Megasphaera species and the available substrates.
For instance, Megasphaera elsdenii preferentially uses the acrylate pathway to produce propionate, an SCFA the liver uses for glucose synthesis. Other Megasphaera species, like M. hexanoica, may use reverse beta-oxidation to produce butyrate and valerate. Butyrate is particularly important as the main energy source for colonocytes, the cells lining the colon, and it supports the integrity of the gut barrier. Valerate production has been positively correlated with the presence of Megasphaera in the gut, especially in individuals consuming fermented dairy products.
Clinical Associations with Human Health
Altered population levels of Megasphaera are consistently observed in individuals with various metabolic and inflammatory conditions. The bacteria are often found at higher abundances in people with obesity or who are overweight, particularly those exhibiting lactate-driven valerate production. This correlation may stem from the bacteria’s metabolic output, as the resulting SCFAs influence host energy regulation and fat storage.
The genus has also been linked to severe intestinal pathologies, including Inflammatory Bowel Disease (IBD) and Colorectal Cancer (CRC). In particular, M. elsdenii is thought to play a concerning role in aggravating inflammation and tumorigenesis. The proposed mechanism involves the bacterium’s ability to trigger an inflammatory response by activating dendritic cells in the colon. This is achieved through specific bacterial components, such as lipopolysaccharide, which initiates an inflammatory cascade that can disrupt the homeostasis of the colon epithelium.
Dietary and Lifestyle Influences
The metabolic activity and population size of Megasphaera are directly responsive to diet. Since Megasphaera relies on lactate produced by other microbes, a diet rich in fermentable fibers and prebiotics can indirectly influence its abundance. The availability of lactose and lactate, such as from fermented dairy, is directly tied to Megasphaera’s valerate production.
Conversely, consumption patterns high in animal protein and alcohol have been associated with a dysbiotic state where Megasphaera species are more prevalent. These dietary elements may favor the proliferation of these specific bacteria. Lifestyle factors such as high psychosocial stress are also linked to general gut dysbiosis, which may indirectly affect the Megasphaera population.