Eubiosis / Homeostasis

Eubiosis / homeostasis refers to a balanced state of gut microbiota. In this state, diverse microbial communities interact in a harmonious manner, contributing to the host's health (8). The balance in the gut lining is kept by ongoing communication between the gut bacteria, immune cells, and the mucosal barrier (16)

Gut homeostasis is established through several key factors (13, 14):
* Nutrition: Plays a crucial role in maintaining balance.
* Metabolite Uptake: Essential for proper gut function.
* Mucosal Barrier Maintenance: Critical for protecting the gut lining.
* Mucosal Immune Regulation: Important for immune system balance.

Under normal physiological conditions, Gut microbiota acts as a homeostatic organ involved in

• the fermentation of complex undigested polysaccharide polymers,


• production of short-chain fatty acids (SCFAs) (digestion),


• synthesis of certain vitamins,


• metabolism of xenobiotics,


• energy production,


• intestinal mucosa integrity, and


• preclusion of pathogenic microbes,


• colonization resistance (1, 2, 3, 4, 5, 17, 18, 19)

Gut tissue must integrate commensal bacteria and maintain their numbers and composition without inducing inflammatory tissue damage (6). Certain members have been reported to have distinct and specific effects on the host immune system, and are considered key to immune homeostasis (20, 21, 22).

• During eubiosis, intestinal epithelial cells (IECs) secrete mucins, antimicrobial peptides (AMPs), and cytokines. The cytokines promote the development of tolerogenic dendritic cells (DCs) and macrophages (9). Epithelial barriers and specific regulatory proteins are essential for maintaining eubiosis. Key regulatory proteins include immunoglobulin A (IgA) (7) and Regenerating islet-derived protein 3 gamma (REG3G) (11)

A balanced intestinal microbiota produces short-chain fatty acids (SCFAs). Bacteria from the phylum Firmicutes/Bacillota are known SCFA producers. SCFAs influence the intestinal immune system in the lamina propria. SCFAs up-regulate anti-inflammatory Treg cells and down-regulate neutrophil migration. Pro-inflammatory and anti-inflammatory cytokines are balanced in systemic circulation and the spleen (10).

SCFAs reduce intracellular reactive oxygen species (ROS) formation. Reduced ROS leads to decreased NFKB signaling activation and less DNA damage (10)

• The balance between CD4+ Th17 cells and Regulatory T Cells (Tregs) is crucial for intestinal homeostasis.(12) CD4+ Th17 cells cells are characterized by pro-inflammatory cytokines (12). CD4+ Th17 cells and ILC3 are activated by specific species of the commensal microbiota during homeostasis. IL-17A and IL-22 are responsible for (15):
  
  
  • Promoting epithelial barrier integrity
  
  
  • Enhancing mucus production
  
  
  • Stimulating the release of anti-microbial peptides
  
  
  
  

Treg cells are characterized by anti-inflammatory cytokines. The normal gut microbiota content directly affects this balance (12)

The gut microbiota ferments complex undigested polysaccharide polymers and produces short-chain fatty acids (SCFAs), synthesizes certain vitamins , contributes to energy production, maintains intestinal mucosa integrity , prevents pathogenic microbes. Gut tissue must integrate commensal bacteria and maintain their numbers and composition without inducing inflammatory tissue damage (6)

References

(1) Flint et al. 2012 Nat Rev Gastroenterol Hepatol 9: 577-589
(2) Shreiner et al. 2015 Curr. Opin. Gastroenterol. 31: 69-75
(3) Wu et al. 2016 Inflamm. Bowel Dis. 22: 1473-1482
(4) Bäumler & Sperandio 2016 Nature 535: 85-93
(5) Torow & Hornef 2017 J. Immunol. 198: 557-563
(6) Littman & Pamer 2011 Cell Host Microbe. 10: 311-323
(7) Perruzza et al. 2017 Cell Rep. 18: 2566-2575
(8) Chen et al. 2024 Front Microbiol 15: 1417864
(9) Wangchuk et al. 2024 Trends in Pharmacological Sciences 45(10): 892-903
(10) Arnone et al. 2021 Front. Nutr. 8: 758518
(11) Rastogi et al. 2020 International Journal of Molecular Sciences 21(9): 3212
(12) Khan et al. 2019 Pathogens 8: 126
(13) Ohtani 2015 Semin Immunopathol 37(1): 65-72
(14) Han et al. 2018b Cancer Management and Research 10: 199-206
(15) Kempski et al. 2017
(16) Roy & Trinchieri 2017
(17) Ley et al. 2008 Nat. Rev. Microbiol. 6: 776–788.
(18) Neish 2009 Gastroenterology. 136: 65–80
(19) Holmes et al. 2011
(20) Koboziev et al. 2014 Free Radic. Biol. Med. 68: 122-133
(21) Arpaia et al. 2013 Nature 504: 451-455
(22) Hooper & Macpherson 2010 Nat. Rev. Immunol. 10: 159-169

see also:
Colonization resistance
Good guys (certain beneficial bacteria)
Gut microbiota & Physical well-being / Health
Intestinal Homeostasis