by Gianfranco Grompone, PhD, Chief Scientific Officer, BioGaia
Microbiome science has reshaped some relevant biological concepts related to host-microbes interactions, establishing new insights on the functional mutualistic relationships between plants, vertebrates and its microbial communities. In this context, humans can be considered as “holobionts” defined as entities comprised of the host and all its symbiotic microbes, including those which have coevolved with it and affect the holobiont’s phenotype1. Recent evidence has positioned probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host2, as examples of such coevolutionary actors of the human-microbes symbiosis.
It is generally accepted that we live now in an Anthropocene era where human activity is heavily impacting planet resources and biodiversity. Human microbiomes are affected by this phenomenon as well and consequences could be related to a chronic loss in microbial ecological diversity, gene richness and available metabolites. In recent centuries, human activity and socio-economic development have been accompanied by a markedly increase in non-communicable diseases such as inflammatory, neurological and metabolic disorders. Strong correlations have been observed between gut microbiome structure and composition and health or disease status, where a common feature to many non-communicable diseases is the loss of gut microbiome’s diversity.
Could probiotics help support the re-introduction of missing microbial species and combat the chronic loss of microbial diversity?
The gut microbiome is acquired at birth and its composition evolves in the first 2-3 years of life, where prenatal and postnatal factors such as mode of delivery, early antibiotic use, diet and feeding mode (formula or breast milk), among others, dynamically shape its composition3. The perinatal period remains then a crucial window of time where key members of the gut microbiome are established and develop a functional interaction with the host immune system3. Tolerance responses to specific antigens are developed during the perinatal period establishing intimate links between gut microbiome structure and composition and immune development3.
Actinobacteria phylum, and especially species belonging to the Bifidobacterium genus, are abundant members of the infant microbiome and their presence in the colon is associated with their active contribution to the metabolism of glycans derived from the diet4. Several bifidobacteria probiotic strains belonging to diverse species such as B. longum, B. breve, B. adolescentis, among others, display Human Milk Oligosaccharides, glycans and mucins degradation capabilities that could have been established upon years of coevolution with the human gut and the human diet4. Besides carbohydrate utilization, surface structures of bifidobacteria such as exopolysaccharides and lipotechoic acids have been shown to establish crucial cross-talks at the interface with innate immune responses. Moreover, bifidobacteria have been shown to establish ecological trophic and cross-feeding interactions with other members of the gut microbiota by enabling short-chain fatty acids and other metabolites in the microbial ecosystem5.
Other examples of mammals’ probiotic gut symbionts are strains belonging to the Lactobacillus genus, comprising diverse species such as, among others, L. reuteri, L. acidophilus, L. rhamnosus, L. gasseri, etc. Among them, Limosilactobacillus reuteri which is found in the digestive tract of diverse mammals6, displays phylogenetic patterns which clearly indicate a host-specific adaptation and stable evolutionary relationships within the human gut, allowing beneficial neuro-immune outcomes to the host7. Some of the physiological implications of these probiotic effects have been established in human clinical trials from a variety of strains belonging to diverse Lactobacillus species.
Based on the available evidence, one can argue that human-adapted lactobacilli and bifidobacteria strains have developed specific “coevolutionary training features” which could explain some of the ecological and physiological positive outcomes in the human host.
Future evidence might progressively support combatting chronic loss of microbial diversity by re-introducing bacterial species such as probiotic strains which coevolved with their human host through our nutrition and may appear as a valid strategy to reduce the risk of chronic disease and infection. This approach should evolve and gain precision from the study of personalized microbiome structure and composition and targeted beneficial impacts in diverse mucosal sites should be further investigated in order to gain maximum benefits.
Understanding how probiotic strains belonging to lactobacilli and bifidobacteria, but in the future also other species, could play a role in the re-introduction of microbial species to re-balance microbiome dysbiosis and potentially restore physiological functions, remains crucial for the coming generations to help prevent future diseases.
- Theis KR, Dheilly NM, Klassen JL, Brucker RM, Baines JF, Bosch TC, Cryan JF, Gilbert SF, Goodnight CJ, Lloyd EA, Sapp J, Vandenkoornhuyse P, Zilber-Rosenberg I, Rosenberg E, Bordenstein SR. Getting the Hologenome Concept Right: an Eco-Evolutionary Framework for Hosts and Their Microbiomes. mSystems. 2016 Mar 29;1(2):e00028-16. doi: 10.1128/mSystems.00028-16. PMID: 27822520; PMCID: PMC5069740.
- Food and Agricultural Organization of the United Nations and World Health Organization. Joint FAO/WHO working group report on drafting guidelines for the evaluation of probiotics in food. Food and Agricultural Organization of the United Nations [online], ftp://ftp.fao.org/es/ esn/food/wgreport2.pdf (2002).
- Peroni DG, Nuzzi G, Trambusti I, Di Cicco ME, Comberiati P Microbiome Composition and Its Impact on the Development of Allergic Diseases. Front Immunol. 2020 Apr 23;11:700. doi: 10.3389/fimmu.2020.00700. eCollection 2020.PMID: 32391012 Review.
- Turroni F, Milani C, Duranti S, Ferrario C, Lugli GA, Mancabelli L, van Sinderen D, Ventura M. Bifidobacteria and the infant gut: an example of co-evolution and natural selection. Cell Mol Life Sci. 2018 Jan;75(1):103-118. doi: 10.1007/s00018-017-2672-0. Epub 2017 Oct 5. PMID: 28983638 Review.
- De Vuyst L, Leroy F. Cross-feeding between bifidobacteria and butyrate-producing colon bacteria explains bifidobacterial competitiveness, butyrate production, and gas production. Int J Food Microbiol. 2011 149:73–80
- Mitsuoka T. The Lactic Acid Bacteria in Health and Disease. Ed Wood BJB (Elsevier Applied Science, London). 1992 pp 69–114.
- Walter J, Britton RA, Roos S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4645-52. doi: 10.1073/pnas.1000099107. Epub 2010 Jun 25. PMID: 20615995; PMCID: PMC3063604.