In a recent study published in Cell Host & Microbe, researchers highlighted the role of lipids, particularly bacterial-derived lipids in the gut microbiome, in mammalian physiology in the context of immunity and metabolism. Commensal fungal species also produce lipid metabolites.
This review compiled the most recently published literature challenging the old theories of how the gut microbiome and the host as a whole interact. They followed the conventional classification of lipids, an exclusion class of biomolecules that include alkyl chain fatty acids and their derivatives found in the bacterial membrane bilayer.
The amount and types of lipids that humans consume have changed dramatically over the past 50 to 100 years. Thus, the authors also addressed how lipid-mediated interactions might help rationalize the drastic increase in inflammatory and autoimmune diseases, as the gut microbiome plays a critical role in the pathogenesis of these diseases.
Finally, they stressed the need for further work in this understudied but fascinating field of biology.
Background
Previous research showed that lipids mainly played a structural role. e.g. in cell membrane. They were also crucial to microbial physiology and interactions between microbes and microbes. However, recent studies have uncovered a bewildering variety of lipid structures and functions, potentially influencing host physiology in health and disease.
Lipids, their biosynthesis and transformation by the gut microbiome
Commensal gut microbes synthesize lipids via de novo biosynthesis and break down dietary lipids to generate secondary metabolites. These metabolites affect host health through their recognition by the immune system, thus affecting numerous metabolic pathways.
Although a large portion of the metabolic content of the gut microbiome (dry weight) consists of lipids, Escherichia coli has been the source of all information on the biosynthesis of gut bacterial lipids. With advances in computational and machine learning approaches, researchers may have a more scalable method for identification of lipids from other types of gut microbiome, for example Bacteroidetes, Firmicutes, Verrucomicrobia and Actinobacteria.
Common lipids in bacterial membranes include phospholipids, glycerolipids, and saccharolipids, such as lipopolysaccharides (LPS). However, some lipids are characteristic of specific bacterial species. For example commensal Bacteroids strains synthesize sphingolipids, such as dihydroceramide (DHCer). Likewise, some anaerobic gut bacteria species and Bacteroids And Firmicutes phyla species synthesize plasmalogens. In addition, some bacteria (eg. Flavobacteria strains) synthesize sulfonolipids.
Each lipid class confers unique structural characteristics and functions on the bacterial membrane. Some lipids also function as signaling molecules sensed by various host receptors, e.g. C-type lectin receptors (CLRs). For example, humans receive exogenous sphingolipids through breast milk, an important determinant of brain development and immunity in the later stages of life.
Similarly, the gut microbiome transforms dietary cholesterol. bacteria sulfonate cholesterol using a gene cluster that harbors the sulfotransferase enzyme. Studies have shown a decrease in this specific gene cluster during intestinal inflammation. Because the biological functions of sulfated cholesterol metabolites from the microbiome are not fully understood, they represent an exciting area for future research. Also, an individual’s gut metagenome could more reliably explain cholesterol, cholesterol derivatives and blood lipid panels, the most commonly used indicators of metabolic health.
Conclusions
Humans consume lipids through food throughout their lives. Eukaryotic cells can synthesize most lipids, except linoleic acid and alpha-linolenic acid, precursors of omega-3 and omega-6 fatty acids. Thus, dietary lipids have various health benefits, for example cell regeneration, membrane stability and maintenance of metabolic pathways.
However, studies have not yet deciphered lipids generated by gut microbiome enzymes and explained their impact on systemic inflammation. Beyond the gut, lipid metabolism in the microbiome can influence chronic inflammation in the brain, potentially leading to many neurodegenerative diseases. Researchers are becoming increasingly interested in investigating whether Parkinson’s disease begins in the gut.
Since the human brain is also rich in sphingolipids and plasmalogens, two gut microbial products, future studies should also evaluate which microbial-derived lipids influence the gut-brain axis. Another area worth exploring is how gut microbiome-driven lipid metabolism is a critical determinant of human health and disease. Preliminary metabolomic profiling studies have shown that the serum of healthy humans contains thousands of bacteria-derived metabolites, many of which may be lipids.
Future efforts should focus on purifying microbiome metabolites and running them for tandem mass spectrometric analysis to generate shared databases. These data can shape strategies for the prevention, diagnosis and treatment of various human diseases in response to the lipids in the human body and help improve clinical outcomes. Individuals can also be subjected to in-depth metabolomic and genetic profiling to link metabolic signatures to microbiome populations.
Further, the scientists should work to develop a catalog of lipid profiles for microbes that correlate with health and disease. Understanding lipid-microbe and host-microbe interactions and genetic engineering of microbial enzymes that mediate lipid metabolism could also be useful, especially for bacterial taxa important to human health, e.g. Lachnospiraceae And Bifidobacteria tribes.
In addition, there is an urgent need to understand outer membrane vesicle (OMV)-mediated lipid secretion and release. It can help develop resistance to viruses or other pathogenic invasions. The researchers emphasized considering the unique lipid fingerprints of gut microbes in future studies assessing human health and disease.