Lamarck's microbiome lowers Darwins Cholesterol


The paper "A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression" published in 2019 by van Passel et al. describes the development of a genetic system for Akkermansia muciniphila, a gut bacterium that has been linked to a number of health benefits. The system allows researchers to manipulate the expression of genes in A. muciniphila, which can be used to study the bacterium's role in gut health.

One of the findings of the study is that A. muciniphila has a number of genes that are involved in the degradation of mucin, a complex sugar that forms a protective layer in the gut. The researchers found that mutants of A. muciniphila that were unable to degrade mucin were unable to colonize the gut. This suggests that mucin foraging is essential for A. muciniphila to establish a stable population in the gut.

The researchers also found that A. muciniphila can influence the expression of genes in the host that are involved in sterol biosynthesis. Sterols are essential for a number of bodily functions, including the production of hormones and the maintenance of cell membranes. The researchers found that A. muciniphila can increase the expression of genes that are involved in the production of cholesterol, a type of sterol. This suggests that A. muciniphila may play a role in regulating cholesterol levels in the host.

The findings of this study provide new insights into the biology of A. muciniphila and its potential role in gut health. The development of a genetic system for A. muciniphila will allow researchers to further study the bacterium and its interactions with the host. This could lead to the development of new treatments for a number of gut-related diseases.

Here are some of the key takeaways from the study:

  • A. muciniphila has a number of genes that are involved in the degradation of mucin.

  • Mucin foraging is essential for A. muciniphila to colonize the gut.

  • A. muciniphila can influence the expression of genes in the host that are involved in sterol biosynthesis.

  • The development of a genetic system for A. muciniphila will allow researchers to further study the bacterium and its interactions with the host.

This study is an important step in the understanding of A. muciniphila and its potential role in gut health. The findings of the study could lead to the development of new treatments for a number of gut-related diseases.

The MUL genes were acquired by horizontal gene transfer (HGT) from other bacteria, without the need for neo-Darwinian mutations. This means that the genes were transferred from one organism to another without the need for those genes to be modified by natural selection.

Neo-Darwinism is a slow process, but the addition of two different organisms evolving symbiotic mechanisms makes it virtually impossible in the 4.5 billion years of Earth's history.

The MUL genes are important for A. muciniphila because they allow the bacteria to repress genes important for cholesterol biosynthesis. This is beneficial for A. muciniphila because cholesterol is a major component of the mucus that lines the gut. By repressing cholesterol biosynthesis, A. muciniphila can reduce the amount of mucus in the gut, which gives it a non Darwinian epigenetic adaptive advantage over other bacteria.

The acquisition of the MUL genes by HGT is an example of how bacteria can acquire new genes and functions without the need for natural selection. This can have a significant impact on the Lamarckian evolution of bacteria.

Here are some additional details about the MUL genes:

  • They are located on two transposable elements (TEs) called mul1 and mul2.

  • The TEs are not essential for A. muciniphila, but they are required for the expression of the MUL genes.

  • The MUL genes are thought to have been acquired from other bacteria in the gut microbiota.

  • The MUL genes are not found in other Akkermansia species, suggesting that they were acquired relatively recently.

The MUL genes are important for repressing genes important for cholesterol biosynthesis. Cholesterol is a type of lipid that is essential for cell function, but too much cholesterol can be harmful. The MUL genes help to keep cholesterol levels in check by repressing the genes that are responsible for making cholesterol.

The acquisition of the MUL genes by A. muciniphila gave the bacterium rapid adaptation (not evolution) via epigenetic phenotypic plasticity. By being able to repress cholesterol biosynthesis, A. muciniphila was able to outcompete other bacteria that were not able to do so. This allowed A. muciniphila to become more abundant in the gut, where it can provide a number of health benefits.

Here are some additional details about the MUL genes:

  • They are located on a mobile genetic element called a transposon.

  • They encode proteins that bind to DNA and repress the transcription of genes.

  • The MUL genes are thought to have been acquired from a different bacterium, possibly a member of the Firmicutes phylum.

  • The acquisition of the MUL genes gave A. muciniphila an adaptive advantage by allowing it to repress cholesterol biosynthesis.


Article snippets:

A genetic system for Akkermansia muciniphila reveals a role for mucin foraging in gut colonization and host sterol biosynthesis gene expression

(2023)

Akkermansia muciniphila, a mucophilic member of the gut microbiota, protects its host against metabolic disorders

Here we developed and applied transposon mutagenesis to identify genes important for intestinal colonization and for the use of mucin.

An analysis of transposon mutants indicated that de novo biosynthesis of amino acids was required for A. muciniphila growth on mucin medium and that many glycoside hydrolases are redundant

We observed that mucin degradation products accumulate in internal compartments within bacteria in a process that requires genes encoding pili and a periplasmic protein complex, which we term mucin utilization locus (MUL) genes.

We determined that MUL genes were required for intestinal colonization in mice but only when competing with other microbes

In germ-free mice, MUL genes were required for A. muciniphila to repress genes important for cholesterol biosynthesis in the colon

Our genetic system for A. muciniphila provides an important tool with which to uncover molecular links between the metabolism of mucins, regulation of lipid homeostasis and potential probiotic activities.


https://www.nature.com/articles/s41564-023-01407-w




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