Current knowledge on the polymicrobial interaction and biofilm between Saccharomyces and Lactobacillaceae: regulatory mechanisms and applications

Abstract

The family Lactobacillaceae plays a crucial role in food fermentation and probiotic applications, and exhibiting metabolic versatility and adaptability to diverse nutrient-rich environments. They are abundant in nutrient-rich environments like fermented food, vegetables, and the vaginal and gastrointestinal tracts of animals, where they metabolize carbohydrates to produce lactic acids. They also produce bioactive compounds and exhibit anti-inflammatory, antibacterial, and antifungal properties. Saccharomyces yeasts are also widely applied in food, medicine, and biofuel industries. Some species, such as S. boulardii, are recognized for their probiotic benefits, particularly in promoting gut health and alleviating intestinal disorders. This review focuses on the polymicrobial interactions between Lactobacillaceae and Saccharomyces species, highlighting their synergistic roles in improving fermentation efficiency, product quality, and microbial stability through mechanisms such as biofilm formation, metabolic exchange, and nutrient sharing. We also discuss competitive interactions observed in certain systems, such as sugarcane fermentation, which demonstrate the complexity of microbial ecology and the need for precise microbial management strategies. By synthesizing current research, this review aims to provide a comprehensive understanding of how microbial interactions influence fermentation outcomes, and to identify existing knowledge gaps and future directions for optimizing industrial applications.

Highlights

• •Lactobacillaceae includes over 300 species crucial for fermentation and probiotics
• •Saccharomyces yeasts are used in food, medicine, and biofuels
• •Polymicrobial interactions enhance fermentation efficiency and product quality
• •Biofilm formation and nutrient sharing boost microbial stability in fermented foods
• •Competitive interactions may reduce ethanol yield in some fermentation processes

1. Introduction

The predominantly non-pathogenic and Gram-positive bacteria in the Lactobacillaceae represent over 300 species belonging to 33 genera [1]. Those genera include Oenococcus, Pediococcus, and Weissella, the genus Paralactobacillus, as well as the genera formerly classified in the family Leuconostocaceae, which was merged with Lactobacillaceae. Another 25 genera were added due to the reclassification of the former genus Lactobacillus in 2020 [2]. These bacteria consist of coccoid or rod-shaped, non-spore-forming, anaerobic cells that colonize nutrient-rich environments, including human food products, animal feed, plants, animals, and humans [2,3]. Some members, especially those who have smaller genomes, have complicated nutritional requirements, and need specific bacteriological media for cultivation. Lactobacillaceae spp. ferment carbohydrates to produce lactate, acetate, and ethanol, which leads to their key traits such as acid production, rapid pH reduction, and competitive growth in acidic and salty environments. Those traits are important for food preservation via fermentation [1,4,5].

The family Lactobacillaceae plays a vital role not only in food fermentation but also in the production of sourdough, meat, vegetable foods, etc [1,6,7]. Lactobacillaceae exhibits a diverse metabolic process, including lipolysis [8], proteolysis [9], bile acid hydrolysis [10], secondary metabolites production [11], and the synthesis of bioactive compounds including vitamins [12]. Furthermore, its applications in bioremediation (e.g., composting), probiotics, and therapeutic applications have been also highlighted in the literature [7,[13], [14], [15], [16]]. In addition, Lactobacillus acidophilus and Saccharomyces cerevisiae have recently been applied in the biotransformation of marine crustacean waste for astaxanthin recovery, achieving comparable yields to chemical extraction while offering a safer and more sustainable alternative [17]. This microbial valorization approach expands the biotechnological relevance of both genera beyond food fermentation into marine waste recycling. The Lactobacillaceae spp. have been reported for shaping microbiomes by inhibiting the proliferation of pathogenic microorganisms in the vagina [18] and gut [19,20] of animals by producing bacteriocins and acidifying the microenvironment [11]. Further, Lactobacillaceae is considered one of the most common and economical bacterial families used as probiotics and ingredients in foods with significant health benefits [21,22]. Here, improving intestinal barrier function and lowering infection risk [23,24], lowering inflammation [25,26], modifying cholesterol and bile acid metabolism Kriaa et al., 2018; [27]), degrading oxalates and lowering the risk of kidney stones [28,29], modulating neurotransmitters related to mood and behavior [[30], [31], [32]], and serving as a modifiable host for the targeted delivery of biotherapeutics [1,33] have been highlighted.

These actions of Lactobacillaceae have been thoroughly investigated in model systems such as Drosophila, bees, and mammals, and clinical research involving humans. With its metabolic flexibility, proven safety profile, and health benefits, The Lactobacillaceae family offers immense potential for transforming the food system to support sustainability, resilience, and the health of societies.

Saccharomyces, a genus within the yeast group that has long played a crucial role in human civilization, belongs to the broader category of yeast whose cellular structure was first described by Nägeli in 1844 [34]. It is widely recognized for its significance in fundamental research, and it has a long history of practical applications and beneficial effects in many disciplines including the food industry, agriculture, medicine, history, and culture. Reflecting its long-standing practical value, Saccharomyces has become a model organism in diverse fields, particularly food fermentation, biotechnology, and biomedical research. Investigations have encompassed whole-genome sequencing, elucidation of metabolic pathways, and optimization of industrial fermentation processes, including bioethanol production [35,36]. Members of the Saccharomyces genus can be ubiquitously found in nature [37,38] and have been isolated from different substrates such as soil around trees, fruits, vineyard grapes, and insects [39]. In addition to the well-known S. cerevisiae, S. eubayanus, S. arboricola, S. kudriavzevii, S. uvarum, S. mikatae, S. jurei, S. paradoxus [[39], [40], [41], [42], [43]], and S. boulardii [37,38] have also been investigated and highlighted in many studies.

S. cerevisiae is the most extensively studied yeast, valued for its numerous biotechnological applications, with a history spanning thousands of years [44]. Its marked properties, such as the ability to ferment sugars into alcohol and CO₂ and the resilience to low pH and high osmolarity conditions, have contributed to its prominent applications in various industries, including food and beverage production as well as biofuel manufacturing [[45], [46], [47]]. Yeast species within the Saccharomyces genus, apart from S. cerevisiae, are less commonly linked to human-directed fermentation. However, many play a role as contributors to interspecies hybrids utilized in beer and wine production [48]. Guan et al. [49] have reported that the hybrids of S. cerevisiae and S. kudriavzevii could be beneficial to very high gravity brewing. S. boulardii has been highlighted in literature for specific probiotic properties, including enhancing intestinal epithelial cell viability, modulating host inflammatory responses, and inhibiting pathogenic bacterial virulence, which support its potential use as a probiotic yeast [50,51]. It has been reported that the clinical activity of S. boulardii is related to recurrent Clostridium difficile intestinal infections and antibiotic-associated diarrhea. Moreover, S. boulardii has been reported to modulate inflammatory pathways, suppress bacterial overgrowth and adherence, stimulate antibody production against toxins, and interfere with inflammatory bowel disease pathogenesis via trapping T cells in mesenteric lymph nodes [52]. Recent research has demonstrated that yeast-derived selenium nanoparticles (YSeNPs), particularly those synthesized by S. cerevisiae, possess significant antiradical and anti-inflammatory activities while maintaining noncytotoxicity at specific doses [53]. These properties highlight the potential of Saccharomyces-based nanomaterials as sustainable therapeutic agents, expanding their applications in biomedicine beyond conventional fermentation roles.

2. Polymicrobial interactions between Saccharomyces and Lactobacillaceae

The coexistence of Saccharomyces yeasts and Lactobacillaceae bacteria underpins many traditional and emerging fermentations. Their interactions are not random but fall into several mechanistic categories: (1) structural association via biofilm or aggregation, (2) nutrient exchange and metabolic cross-feeding, (3) growth modulation including synergism and antagonism, and (4) downstream effects on product functionality Fig. 1.

Fig. 1.

Mechanistic overview of Lactobacillus interactions with Saccharomyces and Candida species. This figure illustrates how Lactobacillus interacts with S. cerevisiae through activation of the lamBDCA quorum-sensing system, which enhances bacterial adhesion and enables partial encapsulation of yeast cells, imposing oxidative stress, nutrient competition, direct contact stimulation and metabolite-derived chemical stress. In S. cerevisiae, these stimuli trigger general stress responses but concurrently downregulate core physiological and signaling pathways—including DNA/RNA/protein synthesis, cell-cycle progression, MAPK signaling and cell-wall integrity—ultimately reducing growth, viability and fermentative capacity. A similar mechanism is observed in interactions with C. albicans, although the fungus exhibits even broader downregulation of cell-cycle, MAPK, osmoregulatory and cell-wall–integrity pathways, leading to more pronounced impairment of survival and physiological function.

Clarifying these levels of interaction helps distinguish species-level processes from their technological outcomes.

2.1. Structural association: biofilm-mediated stability

A key feature of Saccharomyces–Lactobacillaceae consortia is their ability to establish close cell–cell associations, often through lectin-mediated adhesion or dual-species biofilm formation. Such structural organisation stabilises the mixed community and frequently enhances both fermentation robustness and product quality. In kefir fermentation, the co-culture of S. lipolytica with L. kefir relies on lectin-like bacterial surface proteins that mediate aggregation with yeast cells, leading to improved texture, enhanced microbial stability and increased probiotic potential of the final product [54]. Similarly, Lactiplantibacillus plantarum produces lectin-like proteins that bind to the mannan layer of S. cerevisiae, resulting in a stable two-layered polymicrobial biofilm that supports process stability in traditional Fukuyama-pot vinegar production [55,56]. In water kefir, dextran exopolysaccharides secreted by L. hordei promote yeast aggregation and improve matrix quality [57]. Other examples include co-cultures of S. cerevisiae with L. vini, in which bacterial mannose-binding proteins drive the formation of aggregates consisting of a bacterial core surrounded by yeast cells, thereby improving ethanol-fermentation efficiency [56,58]. Co-culturing S. cerevisiae with L. rhamnosus can also increase exopolysaccharide production by 39–42 %, further enhancing microbial stability and process performance [59]. In addition to stabilising cell populations, such structural associations often translate into desirable product attributes. For example, co-fermentation of S. cerevisiae with L. plantarum or Levilactobacillus brevis in Chardonnay-wine production alters aroma profiles in a strain-dependent manner: L. brevis enriches volatile-compound complexity, whereas L. plantarum contributes to a more balanced sensory character [60].

Plant-based substrates also benefit: mixed fermentation of S. cerevisiae and L. plantarum improves gel texture, micro-structure and bioactivity of the matrix [61], while their co-fermentation of persimmon-leaf extract—an agricultural by-product—shows mutualistic growth and enhanced antioxidant activity, supporting value-added up-cycling applications [62]. Likewise, in oyster-juice fermentation this pairing reduces aldehyde-derived off-flavours while enhancing polyunsaturated fatty acids such as DHA and EPA through modulation of phospholipid-metabolism pathways (Li et al., 2024). Taken together, biofilm-mediated and aggregation-driven associations provide both ecological stability for the mixed cultures and measurable improvements in texture, flavour, nutritional and functional qualities of fermented products. The economic importance of such structural cooperation in food fermentations has also been emphasised [63].

2.2. Nutrient exchange and metabolic complementation

Beyond structural association, many cooperative effects are mediated by complementary nutrient supply and metabolic cross-feeding. In sourdough fermentation, S. cerevisiae secretes essential amino acids such as valine and leucine that stimulate the growth of L. brevis subsp. lindneri, thereby influencing fermentation performance [64]. In mixed cultures with L. paracasei, the yeast enhances alcohol and ester formation while the bacterium produces lactic acid, demonstrating reciprocal metabolic contributions to flavour development [65]. Co-cultivation with L. nagelii triggers transcriptomic shifts in yeast carbohydrate metabolism and NAD/NADH homeostasis; S. cerevisiae also releases glutamine, methionine, arginine, histidine and riboflavin that support bacterial growth [66]. A similar mutualistic exchange occurs between S. cerevisiae and L. delbrueckii, where yeast-derived CO₂ and alanine benefit the bacterium, while galactose released by the bacterium supports the yeast [67]. Yeast can additionally improve the survival of L. rhamnosus strains by reducing oxygen and providing metabolites that enhance cell viability, suggesting opportunities to increase probiotic stability in fermented foods [68]. In addition to nutrient complementation through amino acids or paraprobiotic fragments, co-cultivation studies reveal that metabolite exchange between S. cerevisiae and lactobacilli is density- and strain-dependent. For instance, L. plantarum achieved higher biomass yields when co-cultured with S. cerevisiae at a 1:10 yeast-to-bacterium ratio, suggesting enhanced access to yeast-derived nutrients or oxygen-scavenging benefits, whereas at a 1:1 ratio, this advantage was lost. In contrast, L. delbrueckii did not exhibit similar improvements, underscoring that cross-feeding efficiency and metabolic complementation are both context- and species-specific [69]. Interestingly, even inactivated L. paracasei cells or cell fragments can modulate yeast metabolism: supplementation with 10–15 % paraprobiotics derived from L. paracasei MIUG BL 80 has been shown to promote S. cerevisiae multiplication and alcoholic fermentation, while also delaying yeast autolysis during cold storage [70]. These findings extend the concept of metabolic complementation beyond live co-cultures, suggesting that structural components or metabolites from lactic acid bacteria can still exert positive regulatory effects on yeast physiology and fermentation stability.

2.3. Growth modulation: synergistic and antagonistic dynamics

While synergistic interactions are common, certain pairings exhibit competitive or antagonistic behaviours that influence process performance. Co-fermentation of S. cerevisiae with L. plantarum improves gel texture, micro-structure and bioactivity of plant-based matrices [61] and enhances antioxidant activity when applied to persimmon-leaf extract, thereby supporting value-added up-cycling of agricultural by-products [62]. In vivo evidence further supports the synergistic behaviour between L. plantarum and S. boulardii beyond fermentation settings. When administered together in an antibiotic-induced dysbiosis model, the two probiotics restored gut microbial diversity and composition more effectively than single-strain treatments, normalizing the Firmicutes/Bacteroidetes ratio and enhancing mucosal immune defenses, including secretory IgA and β-defensin production. This cooperative modulation of microbial ecology and host immunity illustrates how yeast–lactobacillus consortia can exert complementary benefits extending from metabolic to immunological domains [71]. Recent investigations further demonstrate that growth modulation within S. cerevisiae–Lactobacillus systems is strongly strain- and nutrient-dependent. Specific isolates of L. plantarum and L. brevis stimulate yeast proliferation by releasing amino acids and organic acids that alleviate nitrogen and redox limitations, whereas other lactobacilli impose mild inhibitory effects through acidification and vitamin competition. These strain-specific dynamics highlight a delicate balance between cooperative cross-feeding and competitive exclusion that ultimately determines the stability and productivity of mixed fermentations [72]. A detailed cell-cell interaction study revealed that L. plantarum can inhibit S. cerevisiae growth by up to 80 % without affecting its own proliferation; aggregation with the yeast altered cell-surface roughness and led to partial yeast lysis. Transcriptomic analyses suggested that high cell density in L. plantarum up-regulated the lamBDCA quorum-sensing system, promoting adhesion and coinciding with down-regulation of yeast genes involved in replication, transcription, translation, cell-cycle control, meiosis, several MAPK pathways and key growth-maintenance genes such as ari1, skg6 and kex2/gas1 [73]. Comparable phenomena were observed in L. plantarum–Candida albicans systems, where bacterial aggregation suppressed fungal proliferation and altered stress-response and virulence-related gene expression [74]. In sugarcane ethanol fermentation, antifungal secondary metabolites produced by L. fermentum reduce yeast ethanol yield, whereas organic acids from the yeast suppress L. fermentum growth but favour higher invertase activity [75,76]. These examples demonstrate that the outcome of yeast–lactobacilli co-culture is highly strain- and context-dependent, underlining the need for targeted strain selection and process control.

2.4. Co-culture configurations for biotechnological applications

Process configuration—including inoculation strategy, cell-ratio adjustment and use of immobilised biofilms—offers practical levers to steer mixed-culture behaviour. In prune-wine production, co-versus sequential inoculation of S. cerevisiae with L. paracasei significantly altered phenolic, ester and amino-acid-related metabolite profiles: co-inoculation increased volatile complexity, whereas sequential inoculation reduced grassy notes and improved flavour balance [77]. Immobilised biofilms of S. cerevisiae and L. plantarum on cellulose beads enhance ethanol yield and resistance to contamination, illustrating the advantage of structured cell supports in continuous fermentation [78]. During cereal fermentation, a 2:1 yeast-to-L. helveticus ratio promotes higher alcohol production, with the bacterium contributing proteolytic activity that benefits overall fermentation [79]. Recent work has extended the application of yeast–lactobacillus co-culture systems beyond beverage fermentation to starch-based substrates. Zhao et al. demonstrated that co-fermentation of L. plantarum and S. cerevisiae markedly modified the multiscale structure, physicochemical properties, and digestibility of lotus root starch [61]. Mixed fermentation induced surface cracking and molecular rearrangement of starch granules, promoted the transition from amorphous to crystalline regions, and strengthened hydrogen bonding interactions, leading to enhanced gel viscosity, elasticity, and thermal stability compared with single cultures. These synergistic structural transformations not only improved starch digestibility but also highlighted the potential of yeast–bacteria co-fermentation as a sustainable bioprocess for nutrient enhancement and textural optimization of plant-derived ingredients. In addition to engineered co-culture strategies, naturally evolved microbial consortia also demonstrate the effectiveness of spontaneous mixed fermentations in shaping product quality. A representative example is Shanxi aged vinegar, a traditional Chinese solid-state fermentation system characterized by the coexistence of yeasts, lactic acid bacteria, and acetic acid bacteria throughout different fermentation stages. Comprehensive microbiological profiling identified S. cerevisiae as the dominant yeast during alcoholic fermentation, coexisting with Lactobacillus fermentum, L. plantarum, L. buchneri, L. casei, and Pediococcus spp. as the prevailing lactic acid bacteria, while Acetobacter pasteurianus became predominant during the subsequent acetic fermentation phase. This ecological succession and coexistence of functionally distinct taxa illustrate a naturally optimized process configuration in which yeasts drive alcohol production, lactic acid bacteria modulate acidity and flavour development, and acetic acid bacteria complete the oxidative transformation to acetic acid. Such self-organized, multi-species networks exemplify the metabolic complementarity and resilience achievable without artificial inoculation [80]. Beyond microbial growth dynamics, mixed fermentations of S. cerevisiae and lactobacilli profoundly alter both metabolic and immunological properties of the resulting biomass. GC–MS profiling revealed selective enrichment of short-chain fatty acids, including 2-methylbutyric and butyric acids, in certain co-cultures, suggesting that yeast–bacteria interactions can fine-tune flavor-active and bioactive metabolites. Furthermore, immunomodulation assays using human monocytes demonstrated that while monocultures of either yeast or bacteria induced pro-inflammatory cytokines (TNF-α, IL-6), their co-cultures enhanced anti-inflammatory IL-10 secretion and decreased CD14/CD86 expression, implying synergistic attenuation of immune activation. These findings collectively highlight that yeast–lactobacillus co-cultivation not only optimizes fermentation chemistry but may also enhance the functional and health-promoting value of the products [69]. Consistent findings have been reported by Cherrington et al., who demonstrated that co-cultivation of S. cerevisiae with Lactobacillus species enriched volatile esters, higher alcohols, and organic acids contributing to balanced aroma and flavour profiles [72]. The same co-cultures also showed increased antioxidant capacity and phenolic bioavailability, suggesting that yeast–lactobacillus metabolic interplay can elevate both sensory quality and nutritional functionality of fermented products. These outcomes reinforce the potential of mixed-culture fermentation as a strategy for producing high-value, health-oriented bioproducts.

2.5. Section summary

Across these categories—structural association, metabolic cross-feeding, growth modulation and configuration-driven outcomes—recurrent patterns emerge.

• (1)biofilm- and aggregation-mediated physical stability,
• (2)complementary nutrient exchange supporting mutual growth, and
• (3)strain-dependent positive or negative impacts on product quality and yield.

These mechanistic layers ultimately converge on functional outcomes that determine product performance and bioprocess efficiency. Representative examples summarised in Table 1 highlight how specific Saccharomyces–Lactobacillaceae pairings influence technological traits such as texture, flavour, digestibility, antioxidant capacity, and fermentation stability across different substrates and process configurations. Recognition of these patterns is key to optimizing microbial consortia for predictable industrial performance.

Table 1.

Functional outcomes and process-level implications of Saccharomyces–Lactobacillaceae co-cultures in fermentation systems.

Fermentation system	Microbial combination	Interaction type	Functional or technological outcome	Reference
Wine fermentation	S. cerevisiae – L. paracasei	Co-inoculation vs. sequential inoculation; amino acid and ester exchange	Co-inoculation increased volatile complexity and improved flavour balance	Jiang et al. [77]
Cereal-based fermentation	S. cerevisiae – L. helveticus	Ratio-dependent nutrient complementation	2:1 yeast-to-bacterium ratio improved alcohol yield and proteolytic contribution	Ai et al. [79]
Plant-based matrix (lotus starch)	S. cerevisiae – L. plantarum	Mixed fermentation promoting starch structural rearrangement	Enhanced crystallinity, viscosity, and digestibility; improved gel texture and stability	Zhao et al. [61]
Traditional solid-state fermentation (Shanxi aged vinegar)	S. cerevisiae, Lactobacillus spp., Acetobacter pasteurianus	Spontaneous microbial succession and division of labour	Sequential dominance ensures alcohol, lactic, and acetic acid formation with balanced aroma	Wu et al. [80]
Functional beverage (water kefir/persimmon-leaf extract)	S. cerevisiae – L. plantarum, L. brevis	Mutualistic antioxidant metabolism and EPS production	Increased antioxidant activity and value-added utilization of by-products	Tian et al. [62]
Gut model (in vivo)	S. boulardii – L. plantarum	Cooperative modulation of microbiota and mucosal immunity	Restored microbial balance; elevated sIgA and β-defensin; anti-inflammatory effects	Ruliatna et al. [71]
Continuous bioprocess system	Immobilised S. cerevisiae – L. plantarum biofilm	Structured cell support improving metabolic exchange and contamination resistance	Increased ethanol yield and process stability	Abe et al. [78]
Mixed fermentation of aromatic beverages	S. cerevisiae – Lactobacillus spp.	Metabolic interplay affecting volatiles and phenolics	Enriched esters, higher alcohols, and phenolic bioavailability; enhanced antioxidant activity	Cherrington et al. [72]; Nenciarini et al. [69]

3. Applications of Saccharomyces–Lactobacillaceae polymicrobial systems

Saccharomyces–Lactobacillaceae consortia underpin a broad spectrum of biotechnological processes ranging from traditional food fermentations to next-generation functional and therapeutic products. In fermented beverages such as wine, beer, cider, kefir, and emerging plant- or seafood-based matrices, their co-existence enhances flavour complexity, nutritional quality, and shelf-life stability. In probiotic formulations, co-culturing enhances viability, gastrointestinal persistence and bioactive-compound synthesis, enabling the development of functional foods. Recent technological advances have further demonstrated that combining L. plantarum with S. boulardii in encapsulated delivery systems can markedly improve probiotic stability and efficacy. For example, microencapsulation of L. plantarum AB6-25 and S. boulardii T8-3C within sodium alginate and demineralised whey powder matrices, supplemented with lactobionic acid, resulted in highly efficient encapsulation (88–99 %) and formation of uniform spherical microcapsules with diameters of 3–10 μm. The double-layered microcapsules maintained therapeutic cell viability under simulated gastrointestinal conditions and preserved probiotic potency for up to 180 days at 4 °C, significantly outperforming free-cell controls. Such hybrid yeast–lactobacillus encapsulation systems offer a promising strategy for developing long-shelf-life functional supplements with improved gastrointestinal survival and controlled release [81]. Recent evidence also highlights their potential in cereal-based fermentations. For instance, co-fermentation of L. plantarum with S. cerevisiae markedly improved the quality attributes of wheat-based steamed bread compared with single-yeast fermentation. The co-cultured starter increased the product's specific volume by approximately 32 %, more than doubled the proportion of resistant starch, and significantly enhanced soluble protein content, particularly in the 30–40 kDa range [18]. These modifications translated into superior textural characteristics and improved nutritional digestibility, demonstrating how rationally designed yeast–lactobacillus systems can enhance both technological performance and health-promoting value in staple food production. Beyond food applications, yeast–lactobacillus consortia have also shown therapeutic potential. Recent investigations revealed that S. cerevisiae CNCM I-3856 and L. rhamnosus GG synergistically inhibit Gardnerella vaginalis biofilm formation and viability, a key factor in bacterial vaginosis pathogenesis [82]. Both strains disrupted preformed biofilms and reduced bacterial cell counts within biofilm matrices, while S. cerevisiae further potentiated the antimicrobial effect of metronidazole. These findings highlight a novel anti-biofilm function of yeast–lactobacillus combinations, extending their use from functional foods to probiotic therapeutics targeting polymicrobial infections. Beyond human nutrition, these interactions support bioethanol production, up-cycling of agricultural by-products and biopreservation, where cross-feeding and biofilm-mediated resilience confer robustness under industrial stress. Tailored co-culture strategies—such as sequential inoculation, fine-tuned strain ratios and immobilised biofilm reactors—allow targeted modulation of metabolite profiles to achieve specific sensory and technological goals. Collectively, these findings underscore the versatility of Saccharomyces–Lactobacillaceae partnerships across nutritional, therapeutic, and industrial domains. Table 2 summarises representative interaction types, underlying mechanisms, and their biotechnological applications.

Table 2.

Interactions and biotechnological applications involving both Saccharomyces spp. and Lactobacillaceae spp. across diverse fields.

Microbial species	Growth	Mechanism/Gene Expression/Protein and Metabolism	Remarks/Results	Reference
S. cerevisiae, and L. plantarum ML11-11	Biofilm	Adhesion occurred by interaction between a lectin-like protein of L. plantarum and mannan of S. cerevisiae, with membrane vesicles formed at the interface.	Double-layered polymicrobial biofilm has formed. Potential in stable fermentation to produce Fukuyama pot vinegar.	[55]
S. cerevisiae PE-2, BG-1, CAT-1, IZ-1904, FLE, and L. fermentum CCT-1407	Co-culture	S. cerevisiae favored L. fermentum contamination for higher invertase activities and decreased Lactobacillus growth by secreting organic acids.	The invertase activity of S. cerevisiae does not influence the levels of contamination by L. fermentum during co-culture fermentation.	[76]
S. cerevisiae TMW 3.221, L. hordei TMW 1.1817, 1.1821, 1.1822, 1.1907, L. nagelii TMW 1.1827	Co-culture	L. hordei produced dextran with specific size and structural organization.	L. hordei cells attached to and induced S. cerevisiae aggregates, with the network formation on hydrophilic surfaces in water kefir.	[57]
S. cerevisiae TMW 3.221 and Lactobacillus nagelii TMW 1.1827.	Co-culture	S. cerevisiae induced changes in the expression of 73 genes, carbohydrate metabolism, and reactions involved in NAD/NADH homeostasis of L. nagelii. Also, S. cerevisiae released glutamine, methionine, arginine, histidine, and riboflavin, which are utilized by L. nagelii.	L. nagelii benefited from S. cerevisiae during co-culture in water kefir.	[59]
S. lipolytica CIDCA and L. kefir CIDCA 8310, -14, −15, −17, −19, −110, −111, −113, −115, −116, −21, −25, −26, −32, −35, −43, −44, −45, −47, and −48	Co-culture	S. lipolytica and L. kefir showed thermolabile non-covalently bound surface molecules involved in their interaction, whereas bacterial S-layer proteins play a key role. Co-aggregating L. kefir strains were also capable of agglutinating human red blood cells, which was not seen after treatment with 5 M-LiCl.	A lectin-like activity of Lactobacillus kefir S-layer surface proteins mediates the aggregation with Saccharomyces lipolytica cells, in fermented products, especially Kefir.	[54]
S. cerevisiae PE-2, and L. fermentum ATCC19255	Co-culture	L. fermentum produces antifungal secondary metabolites.	Viable cells and ethanol yield of S. cerevisiae significantly decreased when with L. fermentum in sugarcane fermentation.	[75]
S. cerevisiae J672, and L. vini 2FLAB5	Co-culture	The attachment of lactic acid bacteria to yeast cells could be ascribed to mannose-binding proteins of the bacteria	L. vini–S. cerevisiae cell aggregates consisted of a bacterial core with an outer layer of yeast cells, in ethanol fermentation.	[58] [56]
S. cerevisiae BY4741, L. plantarum HM23	Biofilm	A washing resistant polymicrobial biofilm of S. cerevisiae and L. plantarum formed on cellulose beads.	S. cerevisiae-L. plantarum biofilm was promising in fermenting ethanol due to its productivity and resistance to contamination.	[78]
S. cerevisiae, L. helveticus KLDS1.9204	Co-culture	L. helveticus showed good proteolytic capability but could not utilize starch.	Cell ratio of S. cerevisiae/L. helveticus 2:1 showed better alcohol production in cereal (malt, maize powder, and rice) fermentation.	[79]
S. cerevisiae S-04, L. paracasei L26	Co-culture	L. paracasei maintained high viable cell counts, indicating species compatibility with Saccharomyces cerevisiae.	L. paracasei produced significant amounts of lactic acid, with a concomitant production of alcohols and esters from S. cerevisiae	[65]
S. cerevisiae, L. rhamnosus ATCC9595, R0011, RW-9595 M	Co-culture	Higher levels of EPS operon expressions were observed in L. rhamnosus in co-culture.	The EPS production of L. rhamnosus was enhanced by 39–42 % during co-culture.	[59]
S. cerevisiae, L. brevis subsp. lindneri	Co-culture	S. cerevisiae secreted valine and leucine.	Saccharomyces cerevisiae enhanced cell yields of L. brevis subsp. lindneri in sourdough.	[64]
S. cerevisiae CEN.PK113-7D	Co-culture	S. cerevisiae supplies CO2 and alanine for L. delbrueckii growth which provides galactose to S. cerevisiae and affects its iron response and lipid metabolism.	Observed either competition of the two microbial species for fatty acids or a response to the ethanol produced by S. cerevisiae.	[67]
S. cerevisiae var. bayanus EC-1118 and L. rhamnosus HN001	Co-culture	Both the S. cerevisiae and its cell-free supernatant enhanced the survival of L. rhamnosus.	Improved viability of L. rhamnosus might involve S. cerevisiae's viability, oxygen removal, and metabolite(s) production.	[68]

4. Conclusion

Polymicrobial interactions between Saccharomyces and Lactobacillaceae —encompassing biofilm-driven structural stability, nutrient cross-feeding and context-dependent synergistic or antagonistic dynamics—are central to determining fermentation efficiency, microbial stability and desired sensory attributes. While cooperative behaviour predominates in traditional fermentations such as kefir and sourdough, competitive effects seen in ethanol and other processes highlight the need for informed strain selection and process management. A mechanistic understanding of these interactions provides a framework for rational consortium design, improved process control and the development of next-generation biotechnological applications.

CRediT authorship contribution statement

Zhenbo Xu: Writing – original draft, Conceptualization. Mahesh Premarathna: Writing – original draft, Conceptualization. Yaqin Li: Writing – review & editing. Xiaomao Yin: Writing – review & editing. Thanapop Soteyome: Writing – review & editing. Junyan Liu: Writing – review & editing. Gamini Seneviratne: Writing – review & editing.

Ethics approval and consent to participate

Not applicable.

Funding

This work was supported by the National Natural Science Foundation of China [grant numbers, 32472465], Guangdong Basic and Applied Basic Research Foundation Natural Science Foundation [grant numbers, 2024A1515010128].

Declaration of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Data availability

Not applicable.