The gut microbiota-that is, the community of microorganisms that inhabits and interacts with the ‘second brain‘-influences the development and homeostasis of the mammalian immune system. A crucial function culpably overlooked in 9 months of TV and media debates on Covid-19, in spite of recommendations that Nobel laureate Luc Montagnier made even before the UN declared a pandemic.
Therefore, the concentration and variety of bacterial species in the microbiota (formerly known as ‘bacterial flora’) help prevent inflammation and immune diseases. Its imbalance, conversely, results in greater vulnerability to numerous diseases. Diet is reconfirmed to be the first medicine, according to the school of Hippocrates. Microbiome-focused interventions also appear promising in the management and treatment of some chronic-degenerative diseases.
Maternal inheritance
Acquisition of the gut microbial heritage occurs at birth, during separation from the mother. The mode of delivery, natural and cesarean, affects the status and composition of the microbiota, among other things. However, the diversity, which is greater in principle in natural childbirth, is unstable and goes on to be implemented in the first few years of life. (1)
Individual variability in the gut microbiota remains high. It tends to stabilize in adulthood to a variable resilience to adversity (e.g., diet, antibiotic treatment) and the passage of age. (2) And to decline in old age, with immunosenescence.
Fig. 1 and 2. Formation of the microbiota in the first year of life and its development and change over time (Peterson et al., 2014)
Microbiome and microbiota
The two terms microbiome and microbiota are often used synonymously, but in reality the meaning is different. In the first case, it refers to the genome of the bacterial population that differentially colonizes the intestinal tract (increasing toward the distal part), which constitutes the microbiota proper. (3)
The size of the microbiome is very large, approximately equal to 150 times the human genome. Thanks to new sequencing technologies (including the 16S ribosomal DNA gene), it is now possible to better identify the species of the phyla Firmicutes and Bacteroidetes (about 92 percent of the gut microbiota), which differ in each individual due to genetic and environmental factors. (4)
Innate and adaptive immunity
The innate immune system produces signals, toward the host, that can influence the composition and function of the gut microbiota. It can promote the development of beneficial microorganisms and help maintain a balanced population, or the opposite. The microbiota in each case helps the innate immune system defend the intestinal invasion from pathogenic microorganisms (colonization resistance). (5)
The composition of the gut microbiota is also capable of influencing the adaptive immune system. Depending on the microbial niche, antigens, and the metabolites they produce, there is an intervention on B cells, T cells, and cytokines that determine pro-inflammatory and immune responses. In case of a failure of the adaptive system to homeostasis with the microbiota, susceptibility to various diseases may increase inside and outside the gut. (6)
Fig. 3. Diseases due to inflammatory disorders established by alterations in the crosstalk between microbiota and immune system, influenced by diet (Thaiss et al., 2016)
Gut dysbiosis and diseases
Dysbiosis has a major impact on health, as several diseases are correlated precisely with an altered microbiota. Gut inflammation leads to the “flowering” of pathogens that normally niche, but the restraining effect of beneficial commensals allows their numbers to increase, leading to the formation of the “inflammabiome” (adaptation and response of bacteria in an inflamed gut) (7)
Commensal bacteria can induce inflammatory responses due to altered lipid metabolism and lead to atherosclerosis. Among the main culprits, lipopolysaccharides (LPS) on the surface of bacteria initiate this mechanism and are linked to diseases such as diabetes and obesity. However, there are other pro-inflammatory molecules (e.g., peptidoglycan) that have bactericidal action against pathogens such as Streptococcus pneumoniae and Staphylococcus aureus. (8)
Other dysbiosis diseases
Other diseases that can be induced by the state of dysbiosis include:
Heart and kidneys. Loss of gut barrier integrity, permeability of pathogens and their toxic metabolites lead to disruption of host-microbiota balance and development of cardiovascular and chronic kidney disease. (9)
Chron’s disease and ulcerative colitis. They are part of inflammatory bowel diseases and are due to excessive mobilization of bacteria in the intestinal wall and difficulty in maintaining the intestinal barrier, co-responsible for intestinal immune defenses, intact (10)
Diet and microbiota
Diet, as seen, is the most effective intervention to ensure the good health of the microbiota and correct any irregularities. An imbalanced diet conversely-in feeding harmful bacteria and/or limiting the concentration and variety of friendly ones-can induce dysbiosis and promote the development of various diseases. (11)
Scientific research has shown numerous correlations between nutrient intakes (e.g., Omega 3, dietary fiber), micronutrients, phytocomplexes (e.g., polyphenols) and improved microbiota health. Resulting in a stronger immune system. For more on this topic, please refer to Volume I – People of our trilogy ‘Covid-19, the ABCs,’ at https://www.greatitalianfoodtrade.it/covid-19-abc-volume-i-persone_1.
Therapies
In recent years, fecal microbiota transplantation has emerged as a very promising technique for the treatment of some diseases, intestinal and otherwise. The microbiota is provided by a donor, often a family member. Its transplantation has a high success rate, in general, to reduce dysbiosis. (12)
Antibiotic resistance, by the way, can also affect pathogenic species in the gut microbiota. Therefore, it became necessary to search for alternative ways to eliminate pathogens. And the use of bacteriophages, viruses that specialize in killing bacteria, has shown promise because of their precision of action, which allows beneficial commensal bacteria not to be harmed. (13)
Fig. 4. Dysbiosis corrective interventions by diet or microbiota modification (Rizzetto et al., 2020)
Dario Dongo and Andrea Adelmo Della Penna
Notes
(1) Peterson et al. (2014). Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota. Clinical and Experimental Immunology 179:363-377, doi:10.1111/cei.12474
(2) Lozupone et al. (2012). Diversity, stability and resilience of the human gut microbiota. Nature 489:220-230, doi: 10.1038/nature11550
(3) Ursell et al. (2012). Defining the human microbiome. Nutrition Reviews 70(1):S38-44, doi:10.1111/j.1753-4887.2012.00493.x
(4) Shi et al. (2017.) Interaction between the gut microbiome and mucosal immune system. Military Medical Research 4:14, doi: 10.1186/s40779-017-0122-9
(5) Thaiss et al. (2016). The microbiome and innate immunity. Nature 535:65-74, doi:10.1038/nature18847
(6) Zhao et al. (2018). Adaptive immune education by gut microbiota antigens. Immunology 154:28-37, doi:10.1111/imm.12896
(7) Stecher (2015). The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection. Microbiology Spectrum 3(3), doi: 10.1128/microbiolspec.MBP-0008-2014
(8) Christiakov et al. (2015). Role of gut microbiota in the modulation of atherosclerosis-associated immune response. Frontiers in Microbiology 6:671, doi:10.3389/fmicb.2015.00671
(9) Suganya et al. (2020). Impact of gut microbiota: How it could play roles beyond the digestive system on development of cardiovascular and renal diseases. Microbial Pathogenesis 104583, https://doi.org/10.1016/j.micpath.2020.104583
(10) Becker et al. (2015). The intestinal microbiota in inflammatory bowel disease. ILAR Journal 56(2):192-204, doi:10.1093/ilar/ilv030
(11) Rizzetto et al. (2018). Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex. Journal of Autoimmunity 92:12-34, https://doi.org/10.1016/j.jaut.2018.05.008
(12) Yeh et al. (2020). Mutual interplay of host immune system and gut microbiota in the immunopathology of atherosclerosis. International Journal of Molecular Sciences 21:8729, doi:10.3390/ijms21228729
(13) Vujkovic-Cvijin et al. (2019). HIV and the gut microbiota: composition, consequences, and avenues for amelioration. Current HIV/AIDS Report 16(3):204-213, doi:10.1007/s11904-019-00441-w
Dario Dongo, lawyer and journalist, PhD in international food law, founder of WIISE (FARE - GIFT - Food Times) and Égalité.
Graduated in Food Technologies and Biotechnologies, qualified food technologist, he follows the research and development area. With particular regard to European research projects (in Horizon 2020, PRIMA) where the FARE division of WIISE Srl, a benefit company, participates.
