May 7, 2024

How diet affects the gut microbiome and its implications for diseases

The interplay between diet, the gut microbiome, and host health is cryptic. Diet can influence microbiome and microbiome can affect disease development.[1]

The gut flora includes:

  • bacteria, 
  • viruses,
  • lower and higher eukaryotes, 
  • fungi, 
  • archaea.  

Pathological imbalance in microbiome or dysbiosis might be an essential risk factor in several disorders including Inflammatory Bowel Diseases (IBDs), colon cancer and multisystem organ failure.

How do alterations of the gut influence autoimmune diseases?

In addition, alterations of the gut microbiota have been commonly found in various autoimmune diseases. Some specific microorganisms within this ecosystem can produce metabolites such as

  • tryptophan (Trp), 
  • bile acid (BA) metabolites, 
  • short-chain fatty acids (SCFAs). 

All these mediators influence the immune system, increasing the release of immunosuppressive and inflammatory cells.[2]

Changes in the composition of the gut microbiota are associated with many human diseases. Homeostasis or dysbiosis cannot be considered only by the presence or absence of specific microbial species. Diet plays an important role; in fact, it can shape the composition of the adult gut microbiota.[3]

Dysbiosis seems to be a determinant factor of systemic and oral diseases such as:

  • neurodegenerative diseases (Parkinson’s disease and Alzheimer’s disease), 
  • cardiovascular diseases (hypertension and atherosclerosis), 
  • metabolic diseases (obesity, diabetes), 
  • non-alcoholic fatty liver disease (NAFLD), 
  • gastrointestinal diseases (inflammatory bowel diseases (IBDs), 
  • and colorectal cancer (CRC). 

These effects on the health of the host can occur through many ways such as energy absorption and the microbiota–gut–brain axis.

Microbiota-brain-gut axis and neurodegenerative diseases

The gut microbiota and the brain communicate with each other and interact through the gut-brain axis, which regulates various physiological processes. Strong evidence suggests the gut microbiota has a role in neurodevelopment through this axis by regulating brain metabolites and influencing neuro-endocrine system associated with stress response, memory capabilities and anxiety.[4] 

The function of bile acids in gut microbiome

Bile acids play an important role in regulating gut microbiome. They flow through the enterohepatic circulation 6–8 times per day and go through microbial transformation by gut microbes. This metabolic process exerts profound effects on the liver, intestinal tissues, and the overall composition of the gut microbiota. Their receptors are highly expressed in the intestine, and they can stimulate the inflammatory responses.[5]

Bile acids interact with their receptors (BARs), which play a key role in maintaining the homeostasis and integrity of the intestinal barrier

The most studied bile acid receptors (BARs) are:

  • Takeda G protein-coupled receptor 5 (TGR5), 
  • farnesoid X receptor (FXR), sphingosine-1-phosphate receptor 2 (S1PR2), 
  • vitamin D receptor (VDR), pregnane X receptor (PXR), 
  • constitutive androstane receptor (CAR). 

BAs acts on these receptors as hormones and can modify:

  • metabolism, 
  • inflammation, 
  • immune homeostasis, 
  • tumorigenesis, 
  • aging,

and other aspects of organism.

In addition, bile acids such as Chenodeoxycholic Acid (CDCA) and Tauroursodeoxycholic Acid (TUDCA) are recognized as key mediators involved in the maintenance of the intestinal barrier integrity, and it known they are supposed to be directly involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), Ulcerative Colitis, Small Intestinal Bacterial Overgrowth-Related Undulating Diarrhea (SUDD) and other intestinal pathologies.

Bile acid (BA) metabolic disorder can be generated by a lot of factors such as

  • stress, 
  • pollution, 
  • drugs, 
  • alcohol intake, 
  • high-fat diet (HFD), 
  • sedentary lifestyle. 

As shown in the infographic above, bile acids metabolic dysregulation may raise cholic acid (CA) and deoxycholic acid (DCA) (indicated by ↑), while decreasing chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) (indicated by ↓).

This disproportion in the BA profile can destroy the intestinal barrier, induce pathogen transmigration, and promote immune system activation. This chronic inflammation can evolve in:

  • inflammatory bowel disease (IBD), 
  • sepsis,
  • Nonalcoholic fatty liver disease (NAFLD), 
  • Colorectal cancer (CRC), 
  • age-related immune dysregulation[6]

The intestinal barrier is the largest interface between human and environment, it allows the uptake of nutrients and positively impacts the entire individual, but it is also sensitive to changes in our habits, diet, pollution, and quality of life. 

Irregularities in their composition and in their receptors (BARs) signaling are always associated with intestinal barrier dysfunction. Studying bile acids and their routes might lead to the development of therapies for disorders associated with the degeneration of the intestinal barrier[6]

[1]Perler BK, Friedman ES, Wu GD. The Role of the Gut Microbiota in the Relationship Between Diet and Human Health. Annu Rev Physiol. 2023 Feb 10;85:449-468. doi: 10.1146/annurev-physiol-031522-092054. Epub 2022 Nov 14.

[2]Wang J, Zhu N, Su X, Gao Y, Yang R. Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis. Cells. 2023 Mar 2;12(5):793.

[3]Lee JY, Tsolis RM, Bäumler AJ. The microbiome and gut homeostasis. Science. 2022 Jul;377(6601):eabp9960. 

[4]Wang Q, Yang Q, Liu X. The microbiota-gut-brain axis and neurodevelopmental disorders. Protein Cell. 2023 Oct 25;14(10):762-775. 

[5]Lin S, Wang S, Wang P, Tang C, Wang Z, Chen L, Luo G, Chen H, Liu Y, Feng B, Wu D, Burrin DG, Fang Z. Bile acids and their receptors in regulation of gut health and diseases. Prog Lipid Res. 2023 Jan;89:101210.

[6]Shi L, Jin L, Huang W. Bile Acids, Intestinal Barrier Dysfunction, and Related Diseases. Cells. 2023 Jul 19;12(14):1888.