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 reusearchers  maintain homeostasis [2]. This mutually beneficial relationship is so close that rwesearchers 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 theour 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 rwesearchers 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 theour 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 rwesearchers h 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.