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Botaccini, Francesca et al. ; Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration. © 2012 Bottacini et al. ; This work was financially supported by the Cariparma Bank Foundation to MV. This work was also financially supported by a Federation European Microbiology society (FEMS) Advanced Fellowship 2011 and an Irish Research Council for Science, Engineering & Technology (IRCSET) Embark postdoctoral fellowship to FT. DV is a member of The Alimentary Pharmabiotic Centre and the Alimentary Glycoscience Research Cluster, both funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (grant nos. 07/CE/B1368 and 08/SRC/B1393, respectively). ; Peer Reviewed

Turroni Francesca, Francesca et al. ; [Background] The human gastrointestinal tract (GIT) represents one of the most densely populated microbial ecosystems studied to date. Although this microbial consortium has been recognized to have a crucial impact on human health, its precise composition is still subject to intense investigation. Among the GIT microbiota, bifidobacteria represent an important commensal group, being among the first microbial colonizers of the gut. However, the prevalence and diversity of members of the genus Bifidobacterium in the infant intestinal microbiota has not yet been fully characterized, while some inconsistencies exist in literature regarding the abundance of this genus. ; [Methods/Principal Findings] In the current report, we assessed the complexity of the infant intestinal bifidobacterial population by analysis of pyrosequencing data of PCR amplicons derived from two hypervariable regions of the 16 S rRNA gene. Eleven faecal samples were collected from healthy infants of different geographical origins (Italy, Spain or Ireland), feeding type (breast milk or formula) and mode of delivery (vaginal or caesarean delivery), while in four cases, faecal samples of corresponding mothers were also analyzed. ; [Conclusions] In contrast to several previously published culture-independent studies, our analysis revealed a predominance of bifidobacteria in the infant gut as well as a profile of co-occurrence of bifidobacterial species in the infant's intestine. ; This work was financially supported by the Italian Award for Outstanding Young Researcher scheme "Incentivazione alla mobilità di studiosi stranieri e italiani residenti all'estero" and by the Cariparma Bank Foundation to MV, by Spinner 2013, Regione Emilia Romagna and EF. This work was also financially supported by the FIRB-MIUR NG-LAB Research Program, Project RBLA03ER38_004 to GDB, by a FEMS Advanced Fellowship 2011 and an IRCSET Embark postdoctoral fellowship to FT. DvS and PO are members of The Alimentary Pharmabiotic Centre, which is a Centre for Science and Technology (CSET) funded by the Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (Grant no. 02/CE/B124 and 07/CE/B1368). ; Peer reviewed

CRISPR-Cas systems constitute adaptive immune systems for antiviral defense in bacteria. We investigated the occurrence and diversity of CRISPR-Cas systems in 48 Bifidobacterium genomes to gain insights into the diversity and co-evolution of CRISPR-Cas systems within the genus and investigate CRISPR spacer content. We identified the elements necessary for the successful targeting and inference of foreign DNA in select Type II CRISPRCas systems, including the tracrRNA and target PAM sequence. Bifidobacterium species have a very high frequency of CRISPR-Cas occurrence (77%, 37 of 48). We found that many Bifidobacterium species have unusually large and diverse CRISPR-Cas systems that contain spacer sequences showing homology to foreign genetic elements like prophages. A large number of CRISPR spacers in bifidobacteria show perfect homology to prophage sequences harbored in the chromosomes of other species of Bifidobacterium, including some spacers that self-target the chromosome. A correlation was observed between strains that lacked CRISPR-Cas systems and the number of times prophages in that chromosome were targeted by other CRISPR spacers. The presence of prophage-targeting CRISPR spacers and prophage content may shed light on evolutionary processes and strain divergence. Finally, elements of Type II CRISPR-Cas systems, including the tracrRNA and crRNAs, set the stage for the development of genome editing and genetic engineering tools. © 2015 Briner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ; This study was supported by startup funds from North Carolina State University. The authors thank GenProbio srl for financial support of the Laboratory of Probiogenomics. DvS is a member of the Alimentary pharmabiotic Centre funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (Grant number SFI/12/RC/2273). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Peer Reviewed

Exopolysaccharides (EPS) are surface carbohydrate polymers present in most bacteria acting as a protective surface layer but also interacting with the surrounding environment. This review discusses the roles of EPS synthesized by strains of Lactobacillus and Bifidobacterium, many of them with probiotic characteristics, in the intestinal environment. Current knowledge on genetics and biosynthesis pathways of EPS in lactic acid bacteria and bifidobacteria, as well as the development of genetic tools, has created possibilities to elucidate the interplay between EPS and host intestinal mucosa. These include the microbiota that inhabits this ecological niche and the host cells. Several carbohydrate recognition receptors located in the intestinal epithelium could be involved in the interaction with bacterial EPS and modulation of immune response; however, little is known about the receptors recognizing EPS from lactobacilli or bifidobacteria and the triggered response. On the contrary, it has been clearly demonstrated that EPS play a relevant role in the persistence of the producing bacteria in the intestinal tract. Indeed, some authors postulate that some of the beneficial actions of EPS-producing probiotics could be related to the formation of a biofilm layer protecting the host against injury, for example by pathogens or their toxins. Nevertheless, the in vivo formation of biofilms by probiotics has not been proved to date. Finally, EPS produced by probiotic strains are also able to interact with the intestinal microbiota that populates the gut. In fact, some of these polymers can be used as carbohydrate fermentable source by some gut commensals thus being putatively involved in the release of bacterial metabolites that exert positive benefits for the host. In spite of the increasing knowledge about the role that these surface molecules play in the interaction of probiotic bacteria with the gut mucosal actors, both intestinal receptors and microbiota, the challenging issue is to demonstrate the functionality of EPS in vivo, which will open an avenue of opportunities for the application of EPS-producing probiotics to improve health. ; In the MicroHealth group this research topic is currently financed by the project AGL2015-64901-R (including FEDER European Union funds) from the Ministry of Economy, Industry and Competiveness (MINECO). NC-B acknowledges her FPI fellowship to the MINECO (BES2013-063984). ; Peer reviewed

Bifidobacteria are common and frequently dominant members of the gut microbiota of many animals, including mammals and insects. Carbohydrates are considered key carbon sources for the gut microbiota, imposing strong selective pressure on the complex microbial consortium of the gut. Despite its importance, the genetic traits that facilitate carbohydrate utilization by gut microbiota members are still poorly characterized. Here, genome analyses of 47 representative Bifidobacterium (sub)species revealed the genes predicted to be required for the degradation and internalization of a wide range of carbohydrates, outnumbering those found in many other gut microbiota members. The glycan-degrading abilities of bifidobacteria are believed to reflect available carbon sources in the mammalian gut. Furthermore, transcriptome profiling of bifidobacterial genomes supported the involvement of various chromosomal loci in glycan metabolism. The widespread occurrence of bifidobacterial saccharolytic features is in line with metagenomic and metatranscriptomic datasets obtained from human adult/infant faecal samples, thereby supporting the notion that bifidobacteria expand the human glycobiome. This study also underscores the hypothesis of saccharidic resource sharing among bifidobacteria through species-specific metabolic specialization and cross feeding, thereby forging trophic relationships between members of the gut microbiota. ; We thank GenProbio srl for financial support of the Laboratory of Probiogenomics. This work was financially supported by a FEMS Jensen Award to FT, and by a Ph.D. fellowship (Spinner 2013, Regione Emilia Romagna) to S.D. DvS and FT are members of The APC Microbiome Institute, while DvS is also a member of the Alimentary Glycoscience Research Cluster, both funded by Science Foundation Ireland (SFI), through the Irish Government's National Development Plan (Grant numbers SFI/12/RC/2273 and 08/SRC/B1393, respectively). This work was also partially supported by Fondazione Caritro, by the EU FP7 (PCIG13- GA-2013-618833), and by MIUR "Futuro in Ricerca" E68C13000500001 to NS. Furthermore, this project has been funded in part with funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200900018C. ; Peer Reviewed

Adaptation and tolerance to bile stress are important factors for the survival of bifidobacteria in the intestinal tract. Bifidobacterium animalis is a probiotic microorganism which has been largely applied in fermented dairy foods due to its technological properties and its health-promoting effects for humans. The effect of the presence of bile on the activity and expression of F1F0-ATPase, the pool of ATP and the intracellular pH of B. animalis IPLA 4549 and its mutant with acquired resistance to bile B. animalis 4549dOx was determined. The bile-resistant mutant tolerated the acid pH better than its parent strain. Bile induced the expression of the F1F0-ATPase and increased the membrane-bound H+-ATPase activity, in both parent and mutant strains. In acidic conditions (pH 5.0), the expression and the activity of this enzyme were higher in the mutant than in the parent strain when cells were grown in the absence of bile. Total ATP content was higher for the mutant in the absence of bile, whereas the presence of bile induced a decrease of intracellular ATP levels, which was much more pronounced for the parent strain. At pH 4.0, and independently on the presence or absence of bile, the mutant showed a higher intracellular pH than its parent strain. These findings suggest that the bile-adapted B. animalis strain is able to tolerate bile by increasing the intracellular ATP reserve, and by inducing proton pumping by the F1F0-ATPase, therefore tightly regulating the internal pH, and provide a link between the physiological state of the cell and the response to bile ; This work was financed by European Union FEDER funds and the Spanish Plan Nacional de I + D (AGL2004-06727-C02-01/ALI). B.S. was the recipient of a FPI predoctoral fellowship from the Spanish Ministerio de Educación y Ciencia. ; Peer reviewed

There is a general interest in finding new ways of valorizing fruit and vegetable processing by-products. With this aim, applications of industrial fermentation to improve nutritional value, or to produce biologically active compounds, have been developed. In this sense, the fermentation of a wide variety of by-products including rice, barley, soya, citrus, and milling by-products has been reported. This minireview gives an overview of recent fermentation-based valorization strategies developed in the last 2 years. To aid the designing of new bioprocesses of industrial interest, this minireview also provides a detailed comparison of the fermentation conditions needed to produce specific bioactive compounds through a simple artificial neural network model. Different applications reported have been focused on increasing the nutritional value of vegetable by-products, while several lactic acid bacteria and Penicillium species have been used to produce high purity lactic acid. Bacteria and fungi like Bacillus subtilis, Rhizopus oligosporus, or Fusarium flocciferum may be used to efficiently produce protein extracts with high biological value and a wide variety of functional carbohydrates and glycosidases have been produced employing Aspergillus, Yarrowia, and Trichoderma species. Fermentative patterns summarized may guide the production of functional ingredients for novel food formulation and the development of low-cost bioprocesses leading to a transition toward a bioeconomy model. ; The research performed in the MicroHealth research group was funded by the European Union's Horizon 2020 Research and Innovation Program under grant agreement No. 818368 (MASTER), the project IDI/2018/000236 (funded by PCTI Gobierno del Principado de Asturias/FEDER, UE), and the grant RTI2018-095021-J-I00 (funded by MCIU/AEI/FEDER, UE). CS acknowledges his Postdoctoral research contract funded by the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA). ; Peer reviewed

Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease in humans and is characterized by the presence of hyperactive immune cells and aberrant antibody responses to nuclear and cytoplasmic antigens, including characteristic anti–double-stranded DNA antibodies. We performed a cross-sectional study in order to determine if an SLE-associated gut dysbiosis exists in patients without active disease. A group of 20 SLE patients in remission, for which there was strict inclusion and exclusion criteria, was recruited, and we used an optimized Ion Torrent 16S rRNA gene-based analysis protocol to decipher the fecal microbial profiles of these patients and compare them with those of 20 age- and sex-matched healthy control subjects. We found diversity to be comparable based on Shannon's index. However, we saw a significantly lower Firmicutes/Bacteroidetes ratio in SLE individuals (median ratio, 1.97) than in healthy subjects (median ratio, 4.86; P < 0.002). A lower Firmicutes/Bacteroidetes ratio in SLE individuals was corroborated by quantitative PCR analysis. Notably, a decrease of some Firmicutes families was also detected. This dysbiosis is reflected, based on in silico functional inference, in an overrepresentation of oxidative phosphorylation and glycan utilization pathways in SLE patient microbiota. IMPORTANCE: Growing evidence suggests that the gut microbiota might impact symptoms and progression of some autoimmune diseases. However, how and why this microbial community influences SLE remains to be elucidated. This is the first report describing an SLE-associated intestinal dysbiosis, and it contributes to the understanding of the interplay between the intestinal microbiota and the host in autoimmune disorders. © 2014 Hevia et al. ; This study was financed by European Union FEDER funds and the Spanish Plan Nacional de I+D (grant AGL2010-14952). Arancha Hevia was the recipient of an FPI grant, and Borja Sánchez was the recipient of a Juan de la Cierva postdoctoral contract, both from the Spanish Ministerio de Ciencia e Innovación. ; Peer Reviewed

In this work we analyzed the immune activation properties of different Bifidobacterium strains in order to establish their ability as inductors of specific effector (Th) or regulatory (Treg) responses. First, we determined the cytokine pattern induced by 21 Bifidobacterium strains in peripheral blood mononuclear cells (PBMCs). Results showed that four Bifidobacterium bifidum strains showed the highest production of IL-17 as well as a poor secretion of IFNγ and TNFα, suggesting a Th17 profile whereas other Bifidobacterium strains exhibited a Th1-suggestive profile. Given the key role of Th17 subsets in mucosal defence, strains suggestive of Th17 responses and the putative Th1 Bifidobacterium breve BM12/11 were selected to stimulate dendritic cells (DC) to further determine their capability to induce the differentiation of naïve CD4+ lymphocytes toward different Th or Treg cells. All selected strains were able to induce phenotypic DC maturation, but showed differences in cytokine stimulation, DC treated with the putative Th17 strains displaying high IL-1β/IL-12 and low IL-12/IL-10 index, whereas BM12/11-DC exhibited the highest IL-12/IL-10 ratio. Differentiation of naïve lymphocytes confirmed Th1 polarization by BM12/11. Unexpectedly, any B. bifidum strain showed significant capability for Th17 generation, and they were able to generate functional Treg, thus suggesting differences between in vivo and vitro responses. In fact, activation of memory lymphocytes present in PBMCS with these bacteria, point out the presence in vivo of specific Th17 cells, supporting the plasticity of Treg/Th17 populations and the key role of commensal bacteria in mucosal tolerance and T cell reprogramming when needed. ; This work was financed by European Union FEDER funds and the Spanish Plan Nacional de I+D (grants AGL2007-61805 and AGL2010-14952) and by the Consejo Superior de Investigaciones Científicas (CSIC PIE 200870I049). ; Peer reviewed

Stable isotope labeling of amino acids in cell culture was used for Bifidobacterium longum. A comprehensive proteomic strategy was developed and validated by designing an appropriate semidefined medium that allows stable replacement of natural leucine by [13C6]leucine. Using this strategy, proteins having variations of at least 50% in their expression rates can be quantified with great confidence ; This work was financed by European Union FEDER funds and the Spanish Plan Nacional de I + D (project AGL2004-06727-C02-01/ALI and fellowship PR2006-0421) and by the Swiss National Science Foundation (grant 3100-A0-104214). ; Peer reviewed

Bifidobacteria are commensal microoganisms found in the gastrointestinal tract. Several strains have been attributed beneficial traits at local and systemic levels, through pathogen exclusion or immune modulation, among other benefits. This has promoted a growing industrial and scientific interest in bifidobacteria as probiotic supplements. However, the molecular mechanisms mediating this cross-talk with the human host remain unknown. High-throughput technologies, from functional genomics to transcriptomics, proteomics, and interactomics coupled to the development of both in vitro and in vivo models to study the dynamics of the intestinal microbiota and their effects on host cells, have eased the identification of key molecules in these interactions. Numerous secreted or surface-associated proteins or peptides have been identified as potential mediators of bifidobacteria-host interactions and molecular cross-talk, directly participating in sensing environmental factors, promoting intestinal colonization, or mediating a dialogue with mucosa-associated immune cells. On the other hand, bifidobacteria induce the production of proteins in the intestine, by epithelial or immune cells, and other gut bacteria, which are key elements in orchestrating interactions among bifidobacteria, gut microbiota, and host cells. This review aims to give a comprehensive overview on proteinaceous molecules described and characterized to date, as mediators of the dynamic interplay between bifidobacteria and the human host, providing a framework to identify knowledge gaps and future research needs. ; This research was funded by Grant AGL2013-44039-R from the Spanish "Plan Estatal de I+D+I." LR has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/ under REA grant agreement n°624773. BS was recipient of a Ramón y Cajal postdoctoral contract from the Spanish Ministry of Economy and Competitiveness. SD is hired on a contract supported by BIO2014-55019-JIN project from the Spanish "Plan Estatal de I+D+I." ; Peer Reviewed

An extracellular layer of exopolysaccharides (EPS) covers the surface of some Bifidobacterium animalis subsp. lactis strains, which could be of relevance for its probiotic performance. In order to understand the functional characteristics of B. animalis subsp. lactis, two isogenic strains that differ in their EPS-producing phenotype, due to a single mutation in the gene Balat_1410, were studied. By means of a double crossover recombination strategy, successfully used for the first time in bifidobacteria, Balat_1410 in the type strain B. animalis subsp. lactis DSM10140 was replaced by a mutated gene containing a non-synonymous mutation previously associated with the appearance of a mucoid-ropy phenotype. Nuclear magnetic resonance and SEC-MALS analyses showed that the novel strain harboring the mutation acquired a ropy phenotype, due to the production of a high molecular weight (HMW)-EPS that is not produced in the wild-type strain. Fluorescence labeling of both strains with two fluorescent proteins, m-Cherry and Green Fluorescent Protein, was achieved by expressing the corresponding genes under the control of a native selected promoter (the elongation factor Tu promoter). Remarkably, qualitative and quantitative fluorescence analyses demonstrated that the ropy strain displays a lower capability to adhere to human intestinal epithelial cells. In addition, the presence of the HMW-EPS reduced the capability of the producing strain to form biofilms upon three different abiotic surfaces. This work also highlights the fact that different EPS confer variable functional characteristics to the bifidobacterial surface, which may be relevant for the performance of B. animalis subsp. lactis as a probiotic. The construction of molecular tools allowing the functional characterization of surface structures in next generation probiotics is still a challenging issue that deserves further attention, given the relevant role that such molecules must play in the interaction with the host. ; This work was financed by the Spanish Ministry of Economy and Competitiveness (MINECO) and FEDER European Union funds through the project AGL2015-64901-R. NC-B acknowledges her FPI (BES-2013-063984) fellowship to MINECO ; Peer reviewed

Intestinal dysbiosis, characterized by a reduced Firmicutes/Bacteroidetes ratio, has been reported in systemic lupus erythematosus (SLE) patients. In this study, in vitro cultures revealed that microbiota isolated from SLE patient stool samples (SLE-M) promoted lymphocyte activation and Th17 differentiation from naïve CD4+ lymphocytes to a greater extent than healthy control-microbiota. Enrichment of SLE-M with Treg-inducing bacteria showed that a mixture of two Clostridia strains significantly reduced the Th17/Th1 balance, whereas Bifidobacterium bifidum supplementation prevented CD4+ lymphocyte over-activation, thus supporting a possible therapeutic benefit of probiotics containing Treg-inducer strains in order to restore the Treg/Th17/Th1 imbalance present in SLE. In fact, ex vivo analyses of patient samples showed enlarged Th17 and Foxp3+ IL-17+ populations, suggesting a possible Treg-Th17 trans-differentiation. Moreover, analyses of fecal microbiota revealed a negative correlation between IL-17+ populations and Firmicutes in healthy controls, whereas in SLE this phylum correlated directly with serum levels of IFNγ, a Th1 cytokine slightly reduced in patients. Finally, the frequency of Synergistetes, positively correlated with the Firmicutes/Bacteroidetes ratio in healthy controls, tended to be reduced in patients when anti-dsDNA titers were increased and showed a strong negative correlation with IL-6 serum levels and correlated positively with protective natural IgM antibodies against phosphorylcholine. ; This work was supported by European Union FEDER funds, Fondo de Investigación Sanitaria (PI12/00523), Spanish Plan Nacional de I+D (AGL2010-14952 and AGL2013-44039-R) and Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (EQUIP09-19). J.R.-C. is a recipient of a FPU grant from the Spanish Ministerio de Educación, Cultura y Deporte. B.J. and A.H. are recipients of a Ramón y Cajal postdoctoral contract and a FPI grant, respectively, both from the Spanish Ministerio deEconomía y Competitividad. We thank SLE patients and ALAS (Asociación Lúpicos de Asturias) for their continuous encouragement. ; Peer reviewed

Bifidobacterium longum can be isolated from human faeces, some strains being considered probiotics. B. longum NIZO B667 produces an exo-acting α-L-arabinofuranosidase, AbfB, previously purified by us, that releases L-arabinose from arabinan and arabinoxylan. This activity was subjected to two-seven-fold induction by L-arabinose, D-xylose, L-arabitol and xylitol and to repression by glucose. Maximum activity was obtained at 48 h incubation except for D-xylose that was at 24 h. High concentrations (200 mM) of L-arabitol also caused repression of the arabinofuranosidase. A unique band of activity showing the same migration pattern as the purified AbfB was found in zymograms of cell free extracts, indicating that the activity was likely due to this sole enzyme. The assessment of the influence of inducers and repressors on the activity of AbfB and on the expression of the abfB gene by real time PCR indicated that regulation was transcriptional. DNA amplifications using a pair of degenerated primers flanking an internal fragment within α-L-arabinofuranosidase genes of the family 51 of glycoside hydrolases evidenced that these enzymes are widespread in Bifidobacterium. The aminoacidic sequences of bifidobacteria included a fragment of four to six residues in the position 136-141 that was absent in other microorganisms ; This work was financed by European Union FEDER funds and the Spanish Plan Nacional de I + D (project AGL2004-06088-C02-01/ALI). L. Noriega was the recipient of a predoctoral fellowship from Fundación para la investigación Científica y Técnica (FICYT, Asturias, Spain). M. Gueimonde was funded by a Juan de la Cierva postdoctoral contract from the Spanish Ministry of Education and Science. ; Peer reviewed

[Background] Food waste management is a key issue to global food security and friendly environmental governance. Worldwide, one-third of food produced for human consumption is lost or wasted along the food supply chain, primary production and food processing representing the most significant loses. Therefore, the need to achieve zero waste production schemes is becoming a priority to meet Sustainable Development Goals. Increasing evidence points towards vegetable food waste as a rich source of a wide array of carbohydrate structures and fibres providing the opportunity to identify and develop alternative approaches to valorize agro-food waste. ; [Scope and approach] This review describes the valorization of vegetable waste and by-products via production of (novel) substrates targeted to gut microbiota modulation, emphasizing the importance of raw materials and structural-functional properties of carbohydrates. Furthermore, we propose a novel framework for the rational selection of vegetable sources with potential prebiotic activity, based on machine learning and other computational tools applied to available literature and public database information. ; [Key findings and conclusions] Integration of the body of knowledge within the field of vegetable food waste valorization, from different perspectives, allows a rational selection of carbohydrate-based substrates with promising prebiotic activities. By exploring the interactions among dietary fibre and gut microbial ecosystems using computational tools fed with structural, functional and genomic data, we can identify substrates with potential to selectively stimulate gut commensals, in agreement with experimental evidence. Our approach establishes a new framework that can be extended to a wide range of commensal microbes and carbohydrate structures. ; The work in our research groups was funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No 818368 (MASTER), and the grants RTI 2018-095021-J-I00 (funded by (MCIU/AEI/FEDER, UE), AGL 2017-84614-C2-1-R and AGL 2016-78311-R (funded by (MINECO/AEI/FEDER, UE). Carlos Sabater acknowledges his Postdoctoral research contract funded by the Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) and Postdoctoral research contract Juan de la Cierva-Formación from Spanish Ministry of Science and Innovation (FJC 2019-042125-I). ; Peer reviewed