Gut Microbiota in Dysbiosis: Comparison
Please note this is a comparison between Version 2 by Dean Liu and Version 1 by Walter Manucha.

Inflammation and oxidative stress are critical underlying mechanisms associated with COVID-19 that contribute to the complications and clinical deterioration of patients. Additionally, COVID-19 has the potential to alter the composition of patients’ gut microbiota, characterized by a decreased abundance of bacteria with probiotic effects. Interestingly, certain strains of these bacteria produce metabolites that can target the S protein of other coronaviruses, thereby preventing their transmission and harmful effects. At the same time, the presence of gut dysbiosis can exacerbate inflammation and oxidative stress, creating a vicious cycle that perpetuates the disease. Furthermore, it is widely recognized that the gut microbiota can metabolize various foods and drugs, producing by-products that may have either beneficial or detrimental effects. In this regard, a decrease in short-chain fatty acid (SCFA), such as acetate, propionate, and butyrate, can influence the overall inflammatory and oxidative state, affecting the prevention, treatment, or worsening of COVID-19.

  • gut microbiota
  • inflammation
  • immune system
  • COVID-19
  • SARS-CoV-2
  • probiotics

1. Introduction

COVID-19 (by the acronym of Coronavirus Disease of 2019) is a respiratory disease caused by a novel coronavirus (SARS-CoV-2, by the abbreviation of Severe Acute Respiratory Syndrome Coronavirus 2) that continues to affect millions of people worldwide. While most COVID-19 patients experience respiratory symptoms, up to 20% exhibit gastrointestinal symptoms, such as diarrhea [1], suggesting that the gastrointestinal tract is an additional site of SARS-CoV-2 infection apart from the lungs.
SARS-CoV-2 enters host cells by using the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in both the respiratory and gastrointestinal tracts. Consequently, ACE2 plays a significant role in regulating intestinal inflammation and the microbial ecology of the gut.
Since the gastrointestinal tract serves as the largest immune organ in humans and plays a critical role in defending against infections by pathogens, it is crucial to comprehend the impact of SARS-CoV-2 infection on the host’s gut microbiota and its potential long-term effects on human health.

2. General Concept of Gut Microbiota in a Healthy State and in Dysbiosis

The microbiota is a community of live microorganisms (bacteria, viruses, fungi, archaea and protozoa) that inhabit humans and help uresearchers  maintain homeostasis [2]. This mutually beneficial relationship is so close that wresearchers are considered as a “holobiont”, a superorganism made up of the host and the microorganisms that live in symbiosis with it [3]. The concept of microbiome refers to the set of microorganisms, their genes, and derived metabolites in an ecosystem. The human being has about 23,000 genes, while the microbiota contributes a number 150 times greater. Human microbiota consists of the 10–100 trillion symbiotic microbial cells harbored by each person, mainly bacteria [4,5][4][5]. Most of these are in the gut, and more than 90% of the bacteria of ourthe entire organism are found in the colon only [6]. These data are important considering that most of the studies are carried out on fecal samples, which mainly represent the distal intestinal (colonic) microbiota. Thus, fecal specimens are naturally collected, may be sampled repeatedly, and constitute a less invasive procedure than others, such as intestinal biopsy sample collection, luminal brushing, and intestinal fluid aspirate, which are not suitable methods for healthy people [7,8][7][8]. However, it is important to clarify that stool samples do not represent the totality of the microbiota adhered to the intestinal epithelium and that the bacteria of the upper intestinal tracts are not correctly detected [9]. The conformation of the microbiota in each subject is unique and is determined by a multitude of factors, such as the way wresearchers are born, whether it is by vaginal delivery or caesarean section [10], the type of diet [11], drug intake (mainly antibiotics) [12], and even if one lives in an urban or rural environment [13]. The bacteria that predominate in the intestinal microbiota belong to the Bacteroidetes and Firmicutes phyla [14], and in most individuals, the microbiota could be classified into one of three enterotypes according to the dominant genera Bacteroides, Prevotella or Ruminococcus [15], mainly by the effects of diet [16]. Gut microbiota has a profound influence on human physiology and nutrition, and it has been demonstrated to be essential for human life [17]. The more different types of bacteria in the gut and the more evenly distributed they are, the greater the diversity. A diverse microbiome can perform many more functions, making the whole system more stable. In fact, a diverse and balanced intestinal microbiota ensures the correct functioning of the digestive tract, strengthens the immune system, and improves metabolism [18,19][18][19]. Gut microbiota performs a wide variety of biochemical and physiological functions that influence the host’s metabolism [20]. The microorganisms that compose it have various enzymes that make it possible to transform mainly carbohydrates and other nutrients and components of food that cannot be digested or absorbed in the intestine [21]. These are fermented in the colon and the main carbohydrate-derived metabolites are the short-chain fatty acids (SCFA) acetate, propionate, and butyrate [22]. These metabolites play a very important role for human health, highlighting the reinforcement of the intestinal barrier, the nutrition of the protective mucosa of the intestine, improving transit in the large intestine, as well as the balance of blood glucose levels, among others [23]. However, the westernized lifestyle, characterized by a diet with high content in proteins and fats, less physical activity, greater consumption of drugs and greater stress, produces changes in ourthe microbiota that alter its functions [24]. These alterations are known as intestinal dysbiosis and produce a general deterioration in health that manifests itself with symptoms such as diarrhea/constipation, inflammation, fatigue, allergies and even behavior changes. Intestinal dysbiosis has been shown to be behind diseases such as allergies, asthma, inflammatory bowel diseases, cardiovascular and neurodegenerative diseases, or cancer, among others [25,26,27,28,29][25][26][27][28][29]. Obese patients are an example of gut microbiota dysbiosis, showing a decrease in the Bacteroidetes population and a proportional increase in Firmicutes when compared to gut microbiota of non-obese individuals [30]. Also, they present a lower microbial biodiversity compared to normal weight individuals, and with an increase in plasmatic levels of lipopolysaccharides, favoring inflammatory processes. In this sense, the intestinal microbiota could be related to metabolic and trophic functions, secretion of intestinal hormones and regulators of the immune system, in addition to being involved in the regulation of fat deposits in adipose tissue [31]. As wresearche rs have previously mentioned, gut microbiota plays a key role in educating and strengthening the host’s immune system to fight against multiple infections, especially those of viral origin [32]. Gut microbiota composition and its products have a positive impact on the immune system and inflammatory processes. The gut microbiota is not only able to induce anti-inflammatory responses, but also maintains the balance between the pro-inflammatory and anti-inflammatory responses to modulate the immune response against pathogens. Therefore, there is a synergism between the immune system and the gut microbiota, which helps to prevent and adequately manage different infections that may affect the host’s health. Likewise, gut microbiota-derived metabolites are also able to collaborate with the immunomodulatory and anti-viral actions of intestinal microbiota through the inhibition of viral replication and the improvement of immune response by the increase in epithelial endurance and regulatory T cell production [33,34][33][34]. Several authors have suggested the existence of direct communication between gut microbiota and lungs, known as the gut–lung axis, which allows the bidirectional transport of microbial toxins and metabolites synthesized by gut and lung microbiota through the lymphatic and circulatory system [35,36,37][35][36][37]. Therefore, gut microbiota disorders would be responsible for worsening respiratory outcomes such as in a SARS-CoV-2 infection [35,36,37,38,39,40][35][36][37][38][39][40]. Thus, gut microbiota composition may explain, at least in part, the susceptibility, intensity, and prognosis of the infection by SARS-CoV-2 in human patients, which would make gut microbiota intervention an important strategy to resolve or mitigate this pathology.

References

  1. Liang, W.; Feng, Z.; Rao, S.; Xiao, C.; Xue, X.; Lin, Z.; Zhang, Q.; Qi, W. Diarrhoea may be underestimated: A missing link in 2019 novel coronavirus. Gut 2020, 69, 1141–1143.
  2. Baquero, F.; Nombela, C. The microbiome as a human organ. Clin. Microbiol. Infect. 2012, 18 (Suppl. S4), 2–4.
  3. Obrenovich, M.; Jaworski, H.; Tadimalla, T.; Mistry, A.; Sykes, L.; Perry, G.; Bonomo, R.A. The Role of the Microbiota-Gut-Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases. Microorganisms 2020, 8, 784.
  4. Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464, 59–65.
  5. Sender, R.; Fuchs, S.; Milo, R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016, 14, e1002533.
  6. Dieterich, W.; Schink, M.; Zopf, Y. Microbiota in the Gastrointestinal Tract. Med. Sci. 2018, 6, 116.
  7. Tang, Q.; Jin, G.; Wang, G.; Liu, T.; Liu, X.; Wang, B.; Cao, H. Current Sampling Methods for Gut Microbiota: A Call for More Precise Devices. Front. Cell Infect Microbiol. 2020, 10, 151.
  8. Ticinesi, A.; Nouvenne, A.; Tana, C.; Prati, B.; Cerundolo, N.; Miraglia, C.; De' Angelis, G.L.; Di Mario, F.; Meschi, T. The impact of intestinal microbiota on bio-medical research: Definitions, techniques and physiology of a “new frontier”. Acta Biomed. 2018, 89, 52–59.
  9. Zmora, N.; Zilberman-Schapira, G.; Suez, J.; Mor, U.; Dori-Bachash, M.; Bashiardes, S.; Kotler, E.; Zur, M.; Regev-Lehavi, D.; Brik, R.B.; et al. Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell 2018, 174, 1388–1405.e1321.
  10. Zhang, C.; Li, L.; Jin, B.; Xu, X.; Zuo, X.; Li, Y.; Li, Z. The Effects of Delivery Mode on the Gut Microbiota and Health: State of Art. Front. Microbiol. 2021, 12, 724449.
  11. Leeming, E.R.; Johnson, A.J.; Spector, T.D.; Le Roy, C.I. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients 2019, 11, 2862.
  12. Ramirez, J.; Guarner, F.; Bustos Fernandez, L.; Maruy, A.; Sdepanian, V.L.; Cohen, H. Antibiotics as Major Disruptors of Gut Microbiota. Front. Cell Infect Microbiol. 2020, 10, 572912.
  13. Tyakht, A.V.; Alexeev, D.G.; Popenko, A.S.; Kostryukova, E.S.; Govorun, V.M. Rural and urban microbiota: To be or not to be? Gut Microbes 2014, 5, 351–356.
  14. Turnbaugh, P.J.; Ley, R.E.; Mahowald, M.A.; Magrini, V.; Mardis, E.R.; Gordon, J.I. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006, 444, 1027–1031.
  15. Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D.R.; Fernandes, G.R.; Tap, J.; Bruls, T.; Batto, J.M.; et al. Enterotypes of the human gut microbiome. Nature 2011, 473, 174–180.
  16. Wu, G.D.; Chen, J.; Hoffmann, C.; Bittinger, K.; Chen, Y.Y.; Keilbaugh, S.A.; Bewtra, M.; Knights, D.; Walters, W.A.; Knight, R.; et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011, 334, 105–108.
  17. Bäckhed, F.; Ley, R.E.; Sonnenburg, J.L.; Peterson, D.A.; Gordon, J.I. Host-bacterial mutualism in the human intestine. Science 2005, 307, 1915–1920.
  18. Ho, C.T.; Wu, M.S.; Panyod, S.; Chang, A.C.; Isidoro, C.; Sheen, L.Y. Editorial note: Gut microbiota and health. J. Tradit. Complement Med. 2023, 13, 105–106.
  19. Lozupone, C.A.; Stombaugh, J.I.; Gordon, J.I.; Jansson, J.K.; Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature 2012, 489, 220–230.
  20. Rowland, I.; Gibson, G.; Heinken, A.; Scott, K.; Swann, J.; Thiele, I.; Tuohy, K. Gut microbiota functions: Metabolism of nutrients and other food components. Eur. J. Nutr. 2018, 57, 1–24.
  21. Vernocchi, P.; Del Chierico, F.; Putignani, L. Gut Microbiota Metabolism and Interaction with Food Components. Int. J. Mol. Sci. 2020, 21, 3688.
  22. Gentile, C.L.; Weir, T.L. The gut microbiota at the intersection of diet and human health. Science 2018, 362, 776–780.
  23. Fusco, W.; Lorenzo, M.B.; Cintoni, M.; Porcari, S.; Rinninella, E.; Kaitsas, F.; Lener, E.; Mele, M.C.; Gasbarrini, A.; Collado, M.C.; et al. Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients 2023, 15, 2211.
  24. Hou, K.; Wu, Z.X.; Chen, X.Y.; Wang, J.Q.; Zhang, D.; Xiao, C.; Zhu, D.; Koya, J.B.; Wei, L.; Li, J.; et al. Microbiota in health and diseases. Signal Transduct Target Ther. 2022, 7, 135.
  25. Clemente, J.C.; Ursell, L.K.; Parfrey, L.W.; Knight, R. The impact of the gut microbiota on human health: An integrative view. Cell 2012, 148, 1258–1270.
  26. Hemmati, M.; Kashanipoor, S.; Mazaheri, P.; Alibabaei, F.; Babaeizad, A.; Asli, S.; Mohammadi, S.; Gorgin, A.H.; Ghods, K.; Yousefi, B.; et al. Importance of gut microbiota metabolites in the development of cardiovascular diseases (CVD). Life Sci. 2023, 329, 121947.
  27. Verhaar, B.J.H.; Hendriksen, H.M.A.; de Leeuw, F.A.; Doorduijn, A.S.; van Leeuwenstijn, M.; Teunissen, C.E.; Barkhof, F.; Scheltens, P.; Kraaij, R.; van Duijn, C.M.; et al. Gut Microbiota Composition Is Related to AD Pathology. Front. Immunol. 2021, 12, 794519.
  28. Wang, M.; Yang, G.; Tian, Y.; Zhang, Q.; Liu, Z.; Xin, Y. The role of the gut microbiota in gastric cancer: The immunoregulation and immunotherapy. Front. Immunol. 2023, 14, 1183331.
  29. Yao, C.; Li, Y.; Luo, L.; Xie, F.; Xiong, Q.; Li, T.; Yang, C.; Feng, P.M. Significant Differences in Gut Microbiota Between Irritable Bowel Syndrome with Diarrhea and Healthy Controls in Southwest China. Dig. Dis. Sci. 2023, 68, 106–127.
  30. Ley, R.E.; Turnbaugh, P.J.; Klein, S.; Gordon, J.I. Microbial ecology: Human gut microbes associated with obesity. Nature 2006, 444, 1022–1023.
  31. Le Chatelier, E.; Nielsen, T.; Qin, J.; Prifti, E.; Hildebrand, F.; Falony, G.; Almeida, M.; Arumugam, M.; Batto, J.M.; Kennedy, S.; et al. Richness of human gut microbiome correlates with metabolic markers. Nature 2013, 500, 541–546.
  32. Ferreira, C.; Viana, S.D.; Reis, F. Gut Microbiota Dysbiosis-Immune Hyperresponse-Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches. Microorganisms 2020, 8, 1514.
  33. Gautier, T.; David-Le Gall, S.; Sweidan, A.; Tamanai-Shacoori, Z.; Jolivet-Gougeon, A.; Loréal, O.; Bousarghin, L. Next-Generation Probiotics and Their Metabolites in COVID-19. Microorganisms 2021, 9, 941.
  34. Hong, B.S.; Kim, M.R. Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: A literature review. Phys. Act. Nutr. 2021, 25, 1–7.
  35. Biliński, J.; Winter, K.; Jasiński, M.; Szczęś, A.; Bilinska, N.; Mullish, B.H.; Małecka-Panas, E.; Basak, G.W. Rapid resolution of COVID-19 after faecal microbiota transplantation. Gut 2022, 71, 230–232.
  36. McIlroy, J.R.; Mullish, B.H.; Goldenberg, S.D.; Ianiro, G.; Marchesi, J.R. Intestinal microbiome transfer, a novel therapeutic strategy for COVID-19 induced hyperinflammation?: In reply to, ‘COVID-19: Immunology and treatment options’, Felsenstein, Herbert McNamara et al. 2020’. Clin. Immunol. 2020, 218, 108542.
  37. Nejadghaderi, S.A.; Nazemalhosseini-Mojarad, E.; Asadzadeh Aghdaei, H. Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy. Med. Hypotheses 2021, 147, 110476.
  38. Ciacci, P.; Paraninfi, A.; Orlando, F.; Rella, S.; Maggio, E.; Oliva, A.; Cangemi, R.; Carnevale, R.; Bartimoccia, S.; Cammisotto, V.; et al. Endothelial dysfunction, oxidative stress and low-grade endotoxemia in COVID-19 patients hospitalised in medical wards. Microvasc. Res. 2023, 149, 104557.
  39. Tang, L.; Gu, S.; Gong, Y.; Li, B.; Lu, H.; Li, Q.; Zhang, R.; Gao, X.; Wu, Z.; Zhang, J.; et al. Clinical Significance of the Correlation between Changes in the Major Intestinal Bacteria Species and COVID-19 Severity. Engeering 2020, 6, 1178–1184.
  40. Yeoh, Y.K.; Zuo, T.; Lui, G.C.; Zhang, F.; Liu, Q.; Li, A.Y.; Chung, A.C.; Cheung, C.P.; Tso, E.Y.; Fung, K.S.; et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021, 70, 698–706.
More
Video Production Service