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Review  |  Open Access  |  17 Mar 2022

Cross-feeding interactions between human gut commensals belonging to the Bacteroides and Bifidobacterium genera when grown on dietary glycans

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Microbiome Res Rep 2022;1:12.
10.20517/mrr.2021.05 |  © The Author(s) 2022.
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Elements of the human gut microbiota metabolise many host- and diet-derived, non-digestible carbohydrates (NDCs). Intestinal fermentation of NDCs salvages energy and resources for the host and generates beneficial metabolites, such as short chain fatty acids, which contribute to host health. The development of functional NDCs that support the growth and/or metabolic activity of specific beneficial gut bacteria, is desirable, but dependent on an in-depth understanding of the pathways of carbohydrate fermentation. The purpose of this review is to provide an appraisal of what is known about the roles of, and interactions between, Bacteroides and Bifidobacterium as key members involved in NDC utilisation. Bacteroides is considered an important primary degrader of complex NDCs, thereby generating oligosaccharides, which in turn can be fermented by secondary degraders. In this review, we will therefore focus on Bacteroides as an NDC-degrading specialist and Bifidobacterium as an important and purported probiotic representative of secondary degraders. We will describe cross-feeding interactions between members of these two genera. We note that there are limited studies exploring the interactions between Bacteroides and Bifidobacterium, specifically concerning β-glucan and arabinoxylan metabolism. This review therefore summarises the roles of these organisms in the breakdown of dietary fibre and the molecular mechanisms and interactions involved. Finally, it also highlights the need for further research into the phenomenon of cross-feeding between these organisms for an improved understanding of these cross-feeding mechanisms to guide the rational development of prebiotics to support host health or to prevent or combat disease associated with microbial dysbiosis.


Cross-feeding, plant fibre, Bacteroides, Bifidobacterium, gut microbiota, prebiotic


The diverse community of microorganisms that inhabit the human gastrointestinal tract make up the human gut microbiota (HGM)[1]. The HGM consists of protozoa, archaea, eukaryotes, viruses and bacteria, and these organisms have evolved to exist symbiotically within the host, exerting various beneficial roles, including but not limited to, energy retrieval, protection from invading pathogens, maintaining gut homeostasis, and modulating the immune system. The HGM is made up of three main phyla: Firmicutes, Bacteroidetes and Actinobacteria [Figure 1][2].

Cross-feeding interactions between human gut commensals belonging to the <i>Bacteroides</i> and <i>Bifidobacterium</i> genera when grown on dietary glycans

Figure 1. A diagram representing the most abundant microbial components of the human microbiota in the colonic section of the gut.

Changes in the composition of the gut microbiota can be influenced by various factors, such as type of diet, stress or environment, and may result in a so-called state of dysbiosis, an imbalance in the levels of members of the HGM that has been linked to various diseases. Depletion or overabundance of certain bacterial species throughout (part of) an individual’s lifetime may contribute to gut disorders such as inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis[3]. In this sense, it has been shown that a gut microbiota imbalance during infancy can provoke the development of diseases (e.g., auto-immune diseases) at a later life stage[4]. Moreover, metabolic products of the gut microbiota may promote diseases such as colorectal cancer and obesity and can affect signalling pathways within the host.

The complex structural variation of dietary polysaccharides, such as arabinoxylan, arabinogalactan or pectin, is determined by the monosaccharide composition, type of glycosidic linkage, side chains and substitutions[5]. Due to the high degree of structural diversity found among non-digestible carbohydrates (NDCs) that are part of the human diet, efficient metabolism of dietary and host-derived polysaccharides requires an array of highly specific enzymes, that all belong to the so-called Carbohydrate active enzymes (CAZymes)[6]. Host-derived polysaccharides such as mucins or glycosaminoglycans, and diet-derived polysaccharides, which include glucans, xylans, fructans, mannans and galactans, are mostly resistant to degradation by human enzymes and therefore they form fermentable substrates for members of the gut microbiota, especially in the colon[7]. Fermentation of dietary fibre by the gut microbiota typically produces short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, which are taken up by the host and used primarily as an energy source, thereby benefitting host health[8,9]. In addition, Bifidobacterium species produce lactate, as a major metabolic end-product, while some species generate 1,2-propanediol from fucose metabolism, and both of these metabolites can in turn be converted into SCFAs by other gut microbiota members. These metabolites affect various biological processes; in the intestinal lumen SCFAs lower the intestinal pH, which may inhibit the growth of pathogens, while this is also believed to influence the composition of the wider microbial community[10]. In intestinal epithelial cells, butyrate regulates cell proliferation, differentiation and gene expression in a manner associated with antineoplastic transformation. Systemically, propionate and acetate activate the free fatty acid receptors GPR41 and GPR43, which are expressed by enteroendocrine cells lining the gut and are present in other tissues, including adipocytes; these receptors may help to activate anti-inflammatory signalling pathways, control metabolism, and influence appetite and mood[11]. The ability of the resident bacteria in the gut to efficiently metabolize these otherwise indigestible glycans means that they share a symbiotic relationship with the host and with one another as these bacteria must effectively compete for carbohydrate nutrition and so have co-evolved efficient glycan-harvesting strategies.

The Gram-negative Bacteroidetes is one of the main phyla that make up the HGM. A large proportion of the genome of these organisms is dedicated to the metabolism of complex glycans, making them primary glycan degraders in the HGM[12]. Although several Bacteroides species are known to degrade a variety of distinct polysaccharides, there is not a single known species capable of metabolising all main dietary, complex glycans, such as starch, pectin, xylan or beta-glucan. The degradation of such complex carbohydrates is performed by CAZymes, whose encoding genes are arranged into clusters known as polysaccharide utilisation loci (PULs). These PULs encode, in addition to the above mentioned CAZymes [represented by glycoside hydrolases (GHs), polysaccharide lyases and carbohydrate esterases], various other proteins involved in glycan degradation, including cell surface glycan-binding proteins, TonB-dependent transporters, and sensors, which regulate PUL transcription[13]. For example, the first described PUL was the starch utilisation system (Sus-system) of Bacteroides thetaiotaomicron VPI-5182, which has been extensively studied. The cell surface-associated proteins SusE and SusF bind the polysaccharide substrate, thereby facilitating the initial starch degradation by SusG - an amylase enzyme, which is also located at the bacterial cell surface, and which hydrolyses the large polymeric substrate into smaller oligosaccharides. These oligosaccharides are then transported into the periplasmic compartment by the SusC/SusD complex (a TonB-dependent transporter), where they are further degraded into monosaccharides by SusA and SusB glycosidases [Figure 2].

Cross-feeding interactions between human gut commensals belonging to the <i>Bacteroides</i> and <i>Bifidobacterium</i> genera when grown on dietary glycans

Figure 2. (A) A schematic overview of the PUL required for starch utilisation (Sus) in B. thetaiotaomicron VPI-5182. The substrate is bound by lipoproteins at the cell surface, where it is initially degraded to oligosaccharides and then transported to the periplasm, where it is further hydrolysed to monosaccharides which can then be transported into the cytoplasm of the cell. (B) Genomic content of B. thetaiotaomicron VPI-5182 PUL in its action on starch. PUL: Polysaccharide utilisation loci.

Firmicutes and Actinobacteria are the other two main phyla that are resident in the human gut. These phyla represent Gram-positive bacteria that possess different mechanisms for glycan degradation[14]. Gram-positive PULs (gpPULs) have a similar gene content to the PUL systems present in Bacteroidetes. However, gpPULs are devoid of the SusC/D-encoding gene pair that characterises an archetypical PUL[15]. The gpPULs encode proteins such as transporters (commonly ABC-type transporters), regulatory proteins (typically LacI-type regulators) and glycan-degrading enzymes (mostly GHs), and large glycans (i.e., those that have a DP of > 6-7 monosaccharidic moieties) must be degraded by extracellular (or cell envelope-bound) glycoside hydrolases. The resulting oligosaccharides are then typically bound by solute binding proteins associated with an ABC uptake system which internalizes them to be further degraded into monosaccharides.

In the HGM, the phylum Actinobacteria is largely represented by the Bifidobacterium genus. Members of this genus mainly produce lactate, acetate and formate (and sometimes 1,2-propanediol) as products of sugar fermentation in the gut[16]. Analysis of the genomes of Bifidobacterium longum subspecies infantis and Bifidobacterium bifidum show that they encode glycosyl hydrolases that are utilised in the degradation of human milk oligosaccharides[17]. Bifidobacterium species, however, typically degrade glycans with a lower degree of polymerisation than those utilized by Bacteroidetes members.

As mentioned above, Bifidobacterium species are generally able to metabolize a range of oligomeric and rather simple carbohydrates, commonly being unable to metabolise more complex polysaccharides that require extracellular GHs. Studies have reported evidence of cross-feeding behaviour between members of the Bifidobacterium genus with other organisms, thereby allowing the complete metabolism of certain complex glycans[18]. An example of this is the interspecies cross-feeding relationship between Bifidobacterium bifidum and Bifidobacterium breve when co-cultured on sialyllactose[19]. This study showed how Bi. breve was able to cross feed on sialic acid, the product of 3’-sialyllactose degradation by Bi. bifidum. Bifidobacterium species have also been shown to produce metabolites, such as 1,2-propanediol, that can be used by other HGM members, e.g., Lactobacillus spp. or Eubacterium hallii, for cross-feeding purposes[20,21].

This review will focus on the molecular mechanisms underpinning cross-feeding interactions between members of Bacteroides and Bifidobacterium pertinent to the metabolism of dietary glycans, such as arabinoxylans. We selected these two genera because they are extensively studied as primary and secondary degraders of these glycans. Members of the genus Bacteroides have been shown to be glycan generalists that metabolize complex polysaccharides, generating extracellular oligosaccharides, which may be shared with other microbial members in the gut, such as particular Bifidobacterium species. The latter bacteria have been shown to generally act as specialists in the metabolism of oligosaccharides rather than complex intact polysaccharides. In addition, as we stated above, bifidobacteria are considered to represent beneficial microbes supporting human health. Arabinoxylans are present in commonly consumed cereals, like wheat or corn, and the cross-feeding behaviour between these two groups of bacteria demonstrates how they have co-evolved to utilise a varied range of diet and host-derived carbohydrate sources. We will explore both intra- and inter-genus interactions among members of these two genera. Although other metabolites have been shown to be involved in the cooperation or inhibition of different members of gut microbiota, such as 1,2-propanediol or methane, this review will focus on carbohydrates and their metabolic end products.


Microbial communities have evolved a balanced and dynamic network of metabolic interactions, which enable them to adapt and thrive within the human gastrointestinal tract (GIT). The competition for nutrients between members of the HGM has resulted in the evolution of ecological feeding strategies that increase the efficiency of glycan utilisation[22]. Although there are various distinct definitions describing such interactions in literature, Smith et al.[22] have defined bacterial metabolic cross-feeding as “an interaction between bacterial strains in which molecules resulting from the metabolism of one strain are further metabolised by another strain”. The term “microbial syntrophy” is a closely related term to cross-feeding, which describes the obligately mutualistic metabolism of microorganisms whereby processes are carried out through metabolic interactions between organisms that are mutually dependent upon one another[23]. These syntrophic interactions can result in the metabolism of complex molecules, which would otherwise be unable to be degraded by the action of just one organism.

Bacteroides-Bacteroides interactions

The ability of various Bacteroides species to utilise polysaccharides has been well documented[24]. Initial Bacteroides processing of complex NDCs typically results in the extracellular release of polysaccharide breakdown products (PBPs) which then become available to other organisms that are unable to directly metabolise the complex NDC. Rakoff-Nahoum et al.[25] proposed this notion in 2014 and found that various Bacteroides species are able to degrade different plant-derived polysaccharides to varying degrees, thus producing varying amounts of PBPs. Interestingly, they observed that B. ovatus ATCC 8483 and B. vulgatus ATCC 8482 released only oligosaccharide PBPs from xylan breakdown, which contradicts the findings of Salyers et al.[26] in 1981, who previously described the production of xylose on the breakdown of xylan by these organisms. They then performed growth experiments showing that these PBPs were not universally utilised by the non-polysaccharide-utilising organisms meaning that the use is dependent upon the producer strain as well as the PBPs produced. The ability of the non-utilising strains to grow on these PBPs suggests that they possess PULs that encode CAZymes required to metabolise the breakdown products. The observation of amylopectin breakdown in extracellular zones suggests that, as a consequence of releasing PBPs by the utilising strains, GH and PL CAZymes are also secreted. Communication between Gram-negative bacteria via outer membrane vesicles (OMVs) allows for the secretion of enzymes to extracellular regions where polysaccharide degradation can take place. This was demonstrated in[26] using western immunoblot analysis, which revealed that GH and PL enzymes were present in OMVs from B. ovatus ATCC 8483 and that their release supported the growth of B. vulgatus ATCC 8482 on inulin. This evidence is supported by a further study by Rakoff-Nahoum et al.[27] in 2016, which found that there is a co-operation between B. ovatus ATCC 8483, as primary degrader, in the breakdown of inulin releasing two GH enzymes (BACOVA_04502 and BACOVA_04503) that are not necessary for its metabolism. It is thought that B. ovatus ATCC 8483 expresses these enzymes for the purpose of feeding other organisms in its microbial community and that this process was beneficial for B. vulgatus ATCC 8482, which cannot digest inulin. In co-culture, B. vulgatus ATCC 8482 was shown to grow with increased fitness and in return, increased the fitness of B. ovatus ATCC 8483 possibly due to the production of molecules, PBP or other metabolites, that support the growth of B. ovatus ATCC 8483 or by the detoxification of substances that inhibit its growth. These studies highlight the interactions between members of the Bacteroides genus that allow the growth of organisms that do not possess the necessary degradative enzymes for the direct utilisation of certain carbohydrates. These interactions may be key in the establishment of a metabolically dynamic functional community of microorganisms in the human GIT.

Bifidobacterium-Bifidobacterium interactions

Bifidobacterium species have also been known to interact with one another to cooperatively break down carbohydrates[28]. The differing abilities of strains to utilise glycans have been thought to result in the evolution of cross-feeding activities between bifidobacterial strains. Studies have shown that Bifidobacterium species are able to secrete GH enzymes[29]. It is predicted that 10.9% of the GH enzymes encoded by Bifidobacterium are extracellular, of which 24% are predicted to be of the GH43 family, which act as β-xylosidases and α-L-arabinofuranosidases. Extracellular GH enzymes were identified in 43 bifidobacterial species, with the most prevalent being Bifidobacterium biavatii which was identified to secrete 17 GHs, while Bifidobacterium scardovii and Bi. bifidum each secreting 11 GHs[29]. This provides a strong indication for the existence of glycan sharing abilities among bifidobacterial strains. For example, co-cultivation of Bi. bifidum PRL2010 with Bi. breve 12L, Bifidobacterium adolescentis 22L and Bifidobacterium thermophilum JCM1207 supports the growth of Bi. bifidum PRL2010[28]. Furthermore, metabolic activity of Bi. bifidum PRL2010 was enhanced when co-cultivated with these other bifidobacterial strains, and transcription of genes involved in carbohydrate metabolism was enhanced. When grown in monoculture, Bi. bifidum PRL2010 was unable to utilise starch or xylan; however, the growth of PRL2010 was observed when this strain was cultivated together with Bi. breve 12L or Bi. adolescentis 22L. Conversely, a decrease in the growth of Bi. breve 12L and Bi. thermophilum JCM1207 was noted, suggesting that the utilisation of starch or xylan by Bi. bifidum PRL2010, respectively, did not benefit these strains and in fact imposed competitive pressure on these strains. The reduction in lactate and acetate production by Bi. breve 12L when grown in co-culture as opposed to monoculture supports the idea that the growth of this strain is hindered by the presence of another Bifidobacterium species. Transcriptomic analysis showed that the genes encoding an ABC-transporter and an MFS transporter in Bi. bifidum PRL2010 was upregulated when grown in co-culture. It was suggested that this upregulation was due to the production of simple carbohydrates by Bi. breve 12L and Bi. adolescentis 22L, which act as PBPs that can be utilised by Bi. bifidum PRL2010. Interestingly, upregulation of 21 genes of Bi. breve 12L was observed when co-cultures with Bi. bifidum PRL2010 on starch, and 42 genes when grown on xylan. This upregulation provides evidence for a mutualistic relationship between these two strains[28].

In addition to cross feeding on plant-derived glycans, certain members of the Bifidobacterium genus are involved in the metabolism of host-derived glycans and human milk oligosaccharides (HMOs)[19,30](Egan et al.[30], 2014).Bi. breve UCC2003 is a known utiliser of sialic acid, which is a monosaccharide present in mucin and certain HMOs, and which is released by Bi. Bifidum PRL2010 when grown on such carbohydrate substrates due to the particular extracellular GH enzymes[30,31]. The production of sialic acid from the degradation of the HMO 3’ sialyllactose by Bi. bifidum PRL2010 was shown to support the growth of Bi. breve UCC2003[19].

Bacteroides-Bifidobacterium interactions

Research has shown that Bacteroides and Bifidobacterium have a cross-feeding relationship in the utilisation of certain dietary and host-derived carbohydrates[18]. The sharing of partially degraded oligosaccharides, intermediary molecules, and genes by lateral gene transfer, contributes to the metabolic flexibility of the HGM. In 2010, Hehemann et al.[32], proposed that Bacteroides plebeius, a gut bacterium mainly present in the Japanese population, acquired genes from the marine bacterium Zobellia galactanivorans needed for the degradation of an algal polysaccharide, porphyran. This gene transfer was explained because seaweed is a common component of the Japanese diet, and bacteria associated with this nutrient may have been the route by which the novel CAZymes were acquired by Bacteroides plebeius. Bacteroides species often act as primary degraders of complex carbohydrates in the gut, releasing oligosaccharides that then become available for secondary degrader organisms[33]. Such cross-feeding activities are believed to allow less dominant organisms such as Bifidobacterium to utilise glycans as a source of nutrition without becoming completely out-competed by bacterial strains that are present in the gut in much higher numbers.

An investigation into the interactions between members of the Bacteroides and Bifidobacterium genera in the utilisation of different carbon sources was carried out by Rios-Covian et al.[34]. They cultured different combinations of two strains of Bacteroides and two strains of Bifidobacterium using exopolysaccharide, inulin or glucose as the sole carbon source. They found that Bi. longum NB677 and Bi. breve IPLA2004 are able to utilise glucose as a carbon source; however, neither grew on more complex polysaccharides. Conversely, B. thetaiotaomicron DSM 2079 and B. fragilis DSM 2151 were able to utilise all tested carbon sources. The authors found that the growth of B. thetaiotaomicron DSM 2079 on glucose was inhibited by the presence of Bi. breve IPLA2004, suggesting that the interaction between these organisms, when grown on this simple sugar, is not mutualistic. B. fragilis DSM 2151, on the other hand, was shown to increase the fitness of Bi. longum NB677. These results emphasized that the behaviour of co-cultures of different species is not universal and very much depends on the specific bacterial strain/species combination and particular carbon source.

Elsewhere Rogowski et al.[35], 2015 showed that bifidobacterial growth on xylooligosaccharides (XOS) may be supported by Bacteroides species. Notably, Bi. adolescentis ATCC 15703 was unable to utilise xylans, although it can degrade simple XOS such as linear arabino-xylooligosaccharides. These authors showed that xylans can be divided into complex xylan, such as corn bran (CX), which contains several different linkages and distinct monosaccharides, or simple xylan, such as wheat arabinoxylan (WAX), which consists of a smaller number of different monosaccharides and linkages[35]. WAX was degraded by B. ovatus ATCC 8483 using two PULs [Figure 3A and B], and some of the resulting breakdown products were then further metabolised by Bi. adolescentis ATCC 15703. However, this glycan sharing was not observed with CX. The authors of this study suggested that Bi. adolescentis ATCC 15703 lacked the machinery to degrade the PBPs released by B. ovatus ATCC 8483 from CX due to the complexity of these oligosaccharides. Specifically, B. ovatus ATCC 8483 was shown to encode a GH98, which is located at the bacterial cell surface to start degradation of the CX backbone. The authors hypothesized that if the efficient machinery is introduced into Bi. adolescentis ATCC 15703, this bacterium will be able to cross-feed with B. ovatus ATCC 8483, even with complex xylans. To investigate this, they created a mutant strain of B. ovatus ATCC 8483 that lacked a functioning GH98 xylanase CAZyme (ΔGH98), thus preventing the cleavage of the backbone of CX and inhibiting its growth. When the ΔGH98 mutant was co-cultured with wild-type B. ovatus ATCC 8483 on CX media, growth of both strains was observed, which provides evidence that the wild-type strain releases PBPs from the breakdown of CX, which are then utilised by the mutant.

Cross-feeding interactions between human gut commensals belonging to the <i>Bacteroides</i> and <i>Bifidobacterium</i> genera when grown on dietary glycans

Figure 3. (A) A schematic representation of the glucoronoarabinoxylan utilisation system in B. ovatus ATCC 8483. The substrate is bound by lipoproteins at the cell surface where it is primarily degraded to oligosaccharides and then transported to the periplasm where it is further hydrolysed to monosaccharides which can then be transported to the cytoplasm of the cell. (B) Genomic content of B. ovatus ATCC 8483 PUL in its action on corn arabinoxylan.

Further study into the utilisation of XOS by Bacteroides and Bifidobacterium strains in co-culture supported the findings of the previous study by Zeybek et al.[36]. Mono and co-culture fermentation experiments were carried out with various xylans as substrate; Bi. bifidum, Bi. breve, Bi. longum subspecies infantis and Bi. longum subspecies longum were unable to utilise XOS in monoculture; however, Bifidobacterium animalis subsp. lactis was able to grow on XOS but no other xylans. In monoculture, two Bacteroides strains, B. ovatus ATCC 8483 and B. xylanisolvens XB1A, showed good growth on xylose, XOS, beechwood xylan and corncob xylan. In co-culture, in the presence of the Bacteroides strains, Bi. animalis subsp. lactis, showed growth on beechwood and corncob xylans. Bi. bifidum, Bi. breve, Bi. longum subspecies infantis and Bi. longum subspecies longum showed no growth on any of the substrates in co-culture. These results highlight the differences in xylan-type polysaccharide fermentation abilities of different bifidobacterial species as is the case in the degradation of inulin-type fructans observed by Falony et al.[37]. The observed growth of Bi. animalis subsp. lactis, in co-culture, provides evidence for a cross feeding relationship between this species and the Bacteroides. This is likely due to the release of XOS as a PBP on the extracellular hydrolysis of xylan by the Bacteroides species. This released XOS is subsequently utilised by Bi. animalis subsp. lactis. This also provides an explanation for the lack of growth of other Bifidobacterium species in co-culture as they are unable to utilise XOS.

Cross-feeding behaviour between B. cellulosilyticus DSM 14838 and certain bifidobacterial strains was analysed previously[38], where interactions between the assessed strains were observed during cultivation on plant-derived Larch Wood arabinogalactan (LW-AG, Figure 4). This study demonstrated how B. cellulosilyticus DSM 14838 primarily degrades LW-AG to release rhamnose and β-1,3-galactooligosaccharides, the latter being further metabolised by certain bifidobacterial strains. Bi. breve UCC 2003 grown in co-culture with B. cellulosilyticus DSM 14838 was shown to grow on LW-AG as a carbon source, whereas no growth was detected in monoculture, thus revealing a cross-feeding activity between these two organisms. Further investigation showed that the carbohydrates β-1,3-galactobiose and β-1,3-galactotriose are utilised by Bi. breve UCC 2003. In addition to Bi. breve UCC 2003, also Bi. longum subsp. infantis ATCC 15697 was shown to utilise AG-derived oligosaccharides released by B. cellulosilyticus DSM 14838. The bgaA gene was identified in the genome of Bi. breve UCC 2003 and was predicted to encode a GH2 enzyme which is involved in the degradation of β-1,3-galactooligosaccharides. The active site of the BgaA enzyme was identified as being specific to β-1,3-galactobiose and β-1,3-galactotriose. Interestingly, this gene was not identified in other bifidobacterial species examined, including Bi. breve JCM 7017, Bi. bifidum LMG13195, and Bi. longum subsp. longum NCIMB8809, this being consistent with their inability to cross-feed with B. cellulosilyticus DSM14838.

Cross-feeding interactions between human gut commensals belonging to the <i>Bacteroides</i> and <i>Bifidobacterium</i> genera when grown on dietary glycans

Figure 4. Molecular interactions between B. cellulosilyticus DSM 14838 PRL 2010 and Bi. breve UCC2003 when act on larch wood arabinogalactan. B. cellulosilyticus employs a GH43_24 on its surface to break down the complex polymer into smaller oligosaccharides releasing beta-1,3-galactobiose and beta-1,3-galactotriose and rhamnose into the medium. Bi. breve can use these galactooligosaccharides as carbon source degrading them to galactose using a specific GH2 in its cytoplasm. Galactose is later incorporated into the central catabolism of the cell.

Although no cross-feeding interactions were observed, a study by Liu et al.[39] showed how certain Bacteroides and Bifidobacterium species are involved in the breakdown of polysaccharides in co-culture. Three polysaccharide mixtures, made up of different combinations of AX, xyloglucan, β-glucan and pectin, were used as the sole carbon source to perform co-cultivation experiments involving five different bacterial species, including B. ovatus ATCC 8483 and Bi. longum subsp. longum ATCC 15707. Size-exclusion chromatography showed that the observed degradation of the polysaccharides was carried out by B. ovatus ATCC 8483 and Bi. longum subsp. longum ATCC 15707, and the other bacterial species did not utilise these carbohydrates. Further analysis identified the release of oligosaccharides by B. ovatus ATCC 8483 on the hydrolysis of β-glucan; however, these glucooligosaccharides were not utilised by any of the other species in the co-culture. It was found that B. ovatus ATCC 8483 played a key role in the production of the SCFA succinate, which was utilised in the formation of propionate by other members of the co-culture, supporting the claim that Bacteroides species act as primary degraders of polysaccharides. This was also the case in the production of lactate by both B. ovatus ATCC 8483 and Bi. longum subsp. longum ATCC 15707, which was utilised by the other organisms. This study, along with previous studies discussed, highlights how the microorganisms in the human GIT can cooperatively interact in the breakdown of polysaccharides and benefit one another through PBPs and SCFA production as well as providing benefit to the human host.


The abilities of various Bacteroides and Bifidobacterium species to utilise different polysaccharides have been highlighted in this review. The identification of polysaccharide utilisation loci in the dominant gut phyla, Bacteroides, has helped to increase knowledge of the complex system in which glycan molecules are broken down. It has also allowed for further research into these utilisation mechanisms as well as the ongoing characterisation of carbohydrate-active enzymes that are produced by all glycan-degrading bacteria, including Bifidobacterium. Understanding of enzyme function is essential to fully understand NDC utilisation and may help us predict the production of postbiotics, either SCFA or other bioactive compounds such as vitamins, from a given substrate. Enzymology also contributes to our understanding of the interactions between bacteria in the context of the complex community that is the human gut microbiota.

In the case of Bacteroides and Bifidobacterium, there is evidence for glycan-sharing and cross feeding activities between certain members of these two genera, particularly during the breakdown of dietary fibre. As has been discussed in this review, interactions between these two genera have previously been studied. However, it is likely that many other cross-feeding activities exist that have yet to be discovered. Interaction between Bacteroides and Bifidobacterium in the breakdown of arabinoxylan has been observed in a small number of studies; however, there is little to no literature available on possible cross-feeding activities on other dietary glycans, such as β-glucan, arabinogalactan, arabinan. Future research should investigate the interaction, if any, between Bacteroides and Bifidobacterium in the metabolism of dietary β-glucan and its effect on the human host. In addition, there are numerous other gut commensals, less dominant in the human large intestine such as Lactobacillus reuteri, which can be studied for their cross-feeding activities with Bifidobacterium (either involving dietary fibres or released mon-/oligo-saccharides), but also for the conversion of metabolic end products of one species (e.g., 1,2-propanediol, lactate) into other metabolites (propionate, butyrate). The experimental proof of the conservation of polysaccharide utilisation loci involved in β-glucan degradation specifically, amongst the Bacteroides would allow us to identify the enzymes involved in the metabolism of these molecules, which would then provide a starting point to investigate whether Bifidobacterium has a role in the breakdown of this polysaccharide. Due to the extremely complex nature of the human gut microbiota as well as the complexity and variation in carbohydrate structure, much more research is required for us to fully understand the roles of each of the members of the human gut microbiota.


Author contributions

Writing - original draft preparation: Fernandez-Julia P

Writing - review, editing, and conceptualization: Commane DM, van Sinderen D, Munoz-Munoz J

All authors contributed to the article and approved the submitted version.

Availability of data and materials

Not applicable.

Financial support and sponsorship

Munoz J received financial support from an internal grant in Northumbria University. van Sinderen D is a member of APC Microbiome Ireland which received financial support from Science Foundation Ireland, through the Irish Government’s National Development Plan (SFI/12/RC/2273-P1 and SFI/12/RC/2273-P2).

Conflicts of interest

All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate

Not applicable.

Consent for publication

Not applicable.


© The Author(s) 2022.


1. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J 2017;474:1823-36.

2. Belizário JE, Napolitano M. Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches. Front Microbiol 2015;6:1050.

3. Mar JS, LaMere BJ, Lin DL, et al. Disease severity and immune activity relate to distinct interkingdom gut microbiome states in ethnically distinct ulcerative colitis patients. mBio 2016;7:e01072-16.

4. Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 2018;562:583-8.

5. Hamaker BR, Tuncil YE. A perspective on the complexity of dietary fiber structures and their potential effect on the gut microbiota. J Mol Biol 2014;426:3838-50.

6. Grondin JM, Tamura K, Déjean G, Abbott DW, Brumer H. Polysaccharide utilization loci: fueling microbial communities. J Bacteriol 2017;199:e00860-16.

7. McNeil NI. The contribution of the large intestine to energy supplies in man. Am J Clin Nutr 1984;39:338-42.

8. Le Poul E, Loison C, Struyf S, et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 2003;278:25481-9.

9. Parada Venegas D, De la Fuente MK, Landskron G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol 2019;10:277.

10. Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 2013;54:2325-40.

11. Ang Z, Ding JL. GPR41 and GPR43 in obesity and inflammation - protective or causative? Front Immunol 2016;7:28.

12. Lapébie P, Lombard V, Drula E, Terrapon N, Henrissat B. Bacteroidetes use thousands of enzyme combinations to break down glycans. Nat Commun 2019;10:2043.

13. Larsbrink L, McKee LS, Bacteroidetes bacteria in the soil: Glycan acquisition, enzyme secretion and gliding motility. Adv Appl Microbiol 2020;110:63-98.

14. Koropatkin NM, Cameron EA, Martens EC. How glycan metabolism shapes the human gut microbiota. Nat Rev Microbiol 2012;10:323-35.

15. O Sheridan P, Martin JC, Lawley TD, et al. Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes. Microb Genom 2016;2:e000043.

16. Van der Meulen R, Adriany T, Verbrugghe K, De Vuyst L. Kinetic analysis of bifidobacterial metabolism reveals a minor role for succinic acid in the regeneration of NAD+ through its growth-associated production. Appl Environ Microbiol 2006;72:5204-10.

17. Turroni F, Milani C, Duranti S, Mahony J, van Sinderen D, Ventura M. Glycan utilization and cross-feeding activities by Bifidobacteria. Trends Microbiol 2018;26:339-50.

18. Singh RP. Glycan utilisation system in Bacteroides and Bifidobacteria and their roles in gut stability and health. Appl Microbiol Biotechnol 2019;103:7287-315.

19. Egan M, O’Connell Motherway M, Ventura M, van Sinderen D. Metabolism of sialic acid by Bifidobacterium breve UCC2003. Appl Environ Microbiol 2014;80:4414-26.

20. Turroni F, Özcan E, Milani C, et al. Glycan cross-feeding activities between bifidobacteria under in vitro conditions. Front Microbiol 2015;6:1030.

21. Cheng CC, Duar RM, Lin X, et al. Ecological importance of cross-feeding of the intermediate metabolite 1,2-propanediol between bacterial gut symbionts. Appl Environ Microbiol 2020;86:e00190-20.

22. Smith NW, Shorten PR, Altermann E, Roy NC, Mcnabb WC. The classification and evolution of bacterial cross-feeding. Front Ecol Evol 2019;7:153.

23. Morris BE, Henneberger R, Huber H, Moissl-Eichinger C. Microbial syntrophy: interaction for the common good. FEMS Microbiol Rev 2013;37:384-406.

24. Schwalm ND 3rd, Groisman EA. Navigating the gut buffet: control of polysaccharide utilization in Bacteroides spp. Trends Microbiol 2017;25:1005-15.

25. Rakoff-Nahoum S, Coyne MJ, Comstock LE. An ecological network of polysaccharide utilization among human intestinal symbionts. Curr Biol 2014;24:40-9.

26. Salyers AA, Gherardini F, O’Brien M. Utilization of xylan by two species of human colonic Bacteroides. Appl Environ Microbiol 1981;41:1065-8.

27. Rakoff-Nahoum S, Foster KR, Comstock LE. The evolution of cooperation within the gut microbiota. Nature 2016;533:255-9.

28. Turroni F, Milani C, Duranti S, et al. Deciphering bifidobacterial-mediated metabolic interactions and their impact on gut microbiota by a multi-omics approach. ISME J 2016;10:1656-68.

29. Milani C, Lugli GA, Duranti S, et al. Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut. Sci Rep 2015;5:15782.

30. Egan M, Motherway MO, Kilcoyne M, et al. Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium. BMC Microbiol 2014;14:282.

31. Turroni F, Bottacini F, Foroni E, et al. Genome analysis of Bifidobacterium bifidum PRL2010 reveals metabolic pathways for host-derived glycan foraging. Proc Natl Acad Sci U S A 2010;107:19514-9.

32. Hehemann JH, Correc G, Barbeyron T, Helbert W, Czjzek M, Michel G. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 2010;464:908-12.

33. Fischbach MA, Sonnenburg JL. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 2011;10:336-47.

34. Rios-Covian D, Arboleya S, Hernandez-Barranco AM, et al. Interactions between Bifidobacterium and Bacteroides species in cofermentations are affected by carbon sources, including exopolysaccharides produced by bifidobacteria. Appl Environ Microbiol 2013;79:7518-24.

35. Rogowski A, Briggs JA, Mortimer JC, et al. Glycan complexity dictates microbial resource allocation in the large intestine. Nat Commun 2015;6:7481.

36. Zeybek N, Rastall RA, Buyukkileci AO. Utilization of xylan-type polysaccharides in co-culture fermentations of Bifidobacterium and Bacteroides species. Carbohydr Polym 2020;236:116076.

37. Falony G, Lazidou K, Verschaeren A, Weckx S, Maes D, De Vuyst L. In vitro kinetic analysis of fermentation of prebiotic inulin-type fructans by Bifidobacterium species reveals four different phenotypes. Appl Environ Microbiol 2009;75:454-61.

38. Munoz J, James K, Bottacini F, Van Sinderen D. Biochemical analysis of cross-feeding behaviour between two common gut commensals when cultivated on plant-derived arabinogalactan. Microb Biotechnol 2020;13:1733-47.

39. Liu Y, Heath AL, Galland B, et al. Substrate use prioritization by a coculture of five species of gut bacteria fed mixtures of arabinoxylan, xyloglucan, β-glucan, and pectin. Appl Environ Microbiol 2020;86:e01905-19.

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Fernandez-Julia P, Commane DM, van Sinderen D, Munoz-Munoz J. Cross-feeding interactions between human gut commensals belonging to the Bacteroides and Bifidobacterium genera when grown on dietary glycans. Microbiome Res Rep 2022;1:12.

AMA Style

Fernandez-Julia P, Commane DM, van Sinderen D, Munoz-Munoz J. Cross-feeding interactions between human gut commensals belonging to the Bacteroides and Bifidobacterium genera when grown on dietary glycans. Microbiome Research Reports. 2022; 1(2): 12.

Chicago/Turabian Style

Pedro Fernandez-Julia, Daniel M. Commane, Douwe van Sinderen, Jose Munoz-Munoz. 2022. "Cross-feeding interactions between human gut commensals belonging to the Bacteroides and Bifidobacterium genera when grown on dietary glycans" Microbiome Research Reports. 1, no.2: 12.

ACS Style

Fernandez-Julia, P.; Commane DM.; van Sinderen D.; Munoz-Munoz J. Cross-feeding interactions between human gut commensals belonging to the Bacteroides and Bifidobacterium genera when grown on dietary glycans. Microbiome. Res. Rep. 2022, 1, 12.

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