Explore the vast range of titles available.

Bacteria that have adapted to nutrient-rich, stable environments are typically characterized by reduced genomes. The loss of biosynthetic genes frequently renders these lineages auxotroph, hinging their survival on an environmental uptake of certain metabolites. The evolutionary forces that drive this genome degradation, however, remain elusive. Our analysis of 949 metabolic networks revealed auxotrophies are likely highly prevalent in both symbiotic and free-living bacteria. To unravel whether selective advantages can account for the rampant loss of anabolic genes, we systematically determined the fitness consequences that result from deleting conditionally essential biosynthetic genes from the genomes of Escherichia coli and Acinetobacter baylyi in the presence of the focal nutrient. Pairwise competition experiments with each of 20 mutants auxotrophic for different amino acids, vitamins, and nucleobases against the prototrophic wild type unveiled a pronounced, concentration-dependent growth advantage of around 13% for virtually all mutants tested. Individually deleting different genes from the same biosynthesis pathway entailed gene-specific fitness consequences and loss of the same biosynthetic genes from the genomes of E. coli and A. baylyi differentially affected the fitness of the resulting auxotrophic mutants. Taken together, our findings suggest adaptive benefits could drive the loss of conditionally essential biosynthetic genes.

Akkermansia muciniphila has evolved to specialize in the degradation and utilization of host mucus, which it may use as the sole source of carbon and nitrogen. Mucus degradation and fermentation by A. muciniphila are known to result in the liberation of oligosaccharides and subsequent production of acetate, which becomes directly available to microorganisms in the vicinity of the intestinal mucosa. Coculturing experiments of A. muciniphila with non-mucus-degrading butyrate-producing bacteria Anaerostipes caccae, Eubacterium hallii, and Faecalibacterium prausnitzii resulted in syntrophic growth and production of butyrate. In addition, we demonstrate that the production of pseudovitamin B12 by E. hallii results in production of propionate by A. muciniphila, which suggests that this syntrophy is indeed bidirectional. These data are proof of concept for syntrophic and other symbiotic microbe-microbe interactions at the intestinal mucosal interface. The observed metabolic interactions between A. muciniphila and butyrogenic bacterial taxa support the existence of colonic vitamin and butyrate production pathways that are dependent on host glycan production and independent of dietary carbohydrates. We infer that the intestinal symbiont A. muciniphila can indirectly stimulate intestinal butyrate levels in the vicinity of the intestinal epithelial cells with potential health benefits to the host.IMPORTANCE The intestinal microbiota is said to be a stable ecosystem where many networks between microorganisms are formed. Here we present a proof of principle study of microbial interaction at the intestinal mucus layer. We show that indigestible oligosaccharide chains within mucus become available for a broad range of intestinal microbes after degradation and liberation of sugars by the species Akkermansia muciniphila. This leads to the microbial synthesis of vitamin B12, 1,2-propanediol, propionate, and butyrate, which are beneficial to the microbial ecosystem and host epithelial cells.

All microorganisms release many metabolites, collectively known as the exometabolome. The resultant multi-way cross-feeding of metabolites among microorganisms distributes resources, thereby increasing total biomass of the microbial community, and promotes the recruitment and persistence of phylogenetically and functionally diverse taxa in microbial communities. Metabolite transfer can also select for evolutionary diversification, yielding multiple closely related but functionally distinct strains. Depending on starting conditions, the evolved strains may be auxotrophs requiring metabolic outputs from producer cells or, alternatively, display loss of complementary reactions in metabolic pathways, with increased metabolic efficiency. Metabolite cross-feeding is widespread in many microbial communities associated with animals and plants, including the animal gut microbiome, and these metabolic interactions can yield products valuable to the host. However, metabolite exchange between pairs of intracellular microbial taxa that share the same host cell or organ can be very limited compared to pairs of free-living microorganisms, perhaps as a consequence of host controls over the metabolic function of intracellular microorganisms. Priorities for future research include the development of tools for improved quantification of metabolite exchange in complex communities and greater integration of the roles of metabolic cross-feeding and other ecological processes, including priority effects and antagonistic interactions, in shaping microbial communities. This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.

Cooperation violates the view of \"nature red in tooth and claw\" that prevails in our understanding of evolution, yet examples of cooperation abound. Most work has focused on maintenance of cooperation within a single species through mechanisms such as kin selection. The factors necessary for the evolutionary origin of aiding unrelated individuals such as members of another species have not been experimentally tested. Here, I demonstrate that cooperation between species can be evolved in the laboratory if (1) there is preexisting reciprocation or feedback for cooperation, and (2) reciprocation is preferentially received by cooperative genotypes. I used a two species system involving Salmonella entérica ser. Typhimurium and an Escherichia coli mutant unable synthesize an essential amino acid. In lactose media Salmonella consumes metabolic waste from E. coli, thus creating a mechanism of reciprocation for cooperation. Growth in a spatially structured environment assured that the benefits of cooperation were preferentially received by cooperative genotypes. Salmonella evolved to aid E. coli by excreting a costly amino acid, however this novel cooperation disappeared if the waste consumption or spatial structure were removed. This study builds on previous work to demonstrate an experimental origin of interspecific cooperation, and to test the factors necessary for such interactions to arise.

The human gut microbiota (HGM) makes an important contribution to health and disease. It is a complex microbial community of trillions of microbes with a majority of its members represented within two phyla, the Bacteroidetes and Firmicutes, although it also contains species of Actinobacteria and Proteobacteria. Reflecting its importance, the HGM is sometimes referred to as an 'organ' as it performs functions analogous to systemic tissues within the human host. The major nutrients available to the HGM are host and dietary complex carbohydrates. To utilise these nutrient sources, the HGM has developed elaborate, variable and sophisticated systems for the sensing, capture and utilisation of these glycans. Understanding nutrient acquisition by the HGM can thus provide mechanistic insights into the dynamics of this ecosystem, and how it impacts human health. Dietary nutrient sources include a wide variety of simple and complex plant and animal-derived glycans most of which are not degraded by enzymes in the digestive tract of the host. Here we review how various adaptive mechanisms that operate across the major phyla of the HGM contribute to glycan utilisation, focusing on the most complex carbohydrates presented to this ecosystem.

A co-culture of S. cerevisiae and Y. lipolytica converts low-value biodiesel crude glycerol into isopropanol, a high-value liquid hydrogen carrier.Genetic modifications in S. cerevisiae enhance glycerol utilization, while in Y. lipolytica they redirect metabolism from lipid synthesis to isopropanol production.Cross-feeding synergy uses ethanol from S. cerevisiae as a secondary carbon source, reducing byproducts and improving production efficiency.MiniCbpA-mediated fibrous-bed immobilization enables stable, reusable cell pairing for continuous isopropanol production.The co-culture maintains an 86% yield with industrial crude glycerol, demonstrating resilience and industrial applicability.The modular, scalable platform is adaptable for the biosynthesis of various acetate-derived chemicals. The rapid growth of biodiesel production generates large amounts of crude glycerol, a low-value byproduct with environmental and economic challenges. Here, we present an engineered yeast coculture system combining Saccharomyces cerevisiae and Yarrowia lipolytica to convert crude glycerol into isopropanol, a liquid organic hydrogen carrier. The system integrates metabolic engineering, cell surface display pairing, immobilization, and continuous cultivation in fibrous bed bioreactors. In S. cerevisiae, glycerol use was improved by transporter optimization, pathway redirection, and flux shift from ethanol to isopropanol. In Y. lipolytica, ethanol from S. cerevisiae was redirected to isopropanol by acetyl-CoA reinforcement, malonyl-CoA diversion, and NADPH availability. Optimized pairing and inoculation ratios enhanced stability and yield. The consortia achieved complete glycerol utilization and three reuse cycles over 180 h. With pure glycerol, 28.34 g/l isopropanol was produced, while crude glycerol reached 86.06% of this yield. This strategy offers a scalable, modular route to convert biodiesel byproducts into bioenergy carriers. [Display omitted] Efficient bioconversion of toxic, impurity-rich industrial wastes, particularly crude glycerol, into reusable energy resources remains a major challenge, primarily due to feedstock heterogeneity and intrinsic metabolic limitations in conventional monocultures. Addressing these bottlenecks, our study establishes a robust in situ paired synthetic yeast consortium capable of stable and continuous conversion of crude glycerol into isopropanol, a strategically important liquid organic hydrogen carrier. Based on validated lab-scale proof of concept and functional operation in controlled bioreactors, the Technology Readiness Level (TRL) of this integrated platform is assessed between 3 and 4. To progress toward industrial implementation, further optimization of pilot-scale fermentation, together with the development of cost-effective downstream recovery and purification processes, will be required. Given the growing global demand for sustainable hydrogen logistics and waste valorization, this platform offers a compelling technological route for transforming an abundant, low-value industrial byproduct into a high-impact energy carrier, positioning it as a promising candidate for future circular bioeconomy strategies. Shi et al. engineer a synthetic yeast consortium to valorize crude glycerol, a biodiesel waste, into isopropanol. By integrating metabolic cross-feeding with in situ cell pairing and immobilization, this platform establishes a robust, scalable route for transforming industrial byproducts into sustainable energy resources.

Intestinal barriers play a crucial role in human physiology, both in homeostatic and pathological conditions. Disruption of the intestinal barrier is a significant factor in the pathogenesis of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. The profound influence of the gut microbiota on intestinal diseases has sparked considerable interest in manipulating it through dietary interventions, probiotics, and fecal microbiota transplantation as potential approaches to enhance the integrity of the intestinal barrier. Numerous studies have underscored the protective effects of specific microbiota and their associated metabolites. In recent years, an increasing body of research has demonstrated that Akkermansia muciniphila ( A. muciniphila , Am) plays a beneficial role in various diseases, including diabetes, obesity, aging, cancer, and metabolic syndrome. It is gaining popularity as a regulator that influences the intestinal flora and intestinal barrier and is recognized as a ‘new generation of probiotics’. Consequently, it may represent a potential target and promising therapy option for intestinal diseases. This article systematically summarizes the role of Am in the gut. Specifically, we carefully discuss key scientific issues that need resolution in the future regarding beneficial bacteria represented by Am, which may provide insights for the application of drugs targeting Am in clinical treatment.

Background Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. β -Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction. Results BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis , which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii . A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals. Conclusions These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii –ILA–AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis . BsYQ6kaZHXkFsG8eqgZ27E Video Abstract Graphical Abstract

Microbes in the intestinal tract have a strong influence on human health. Their fermentation of dietary nondigestible carbohydrates leads to the formation of health-promoting short-chain fatty acids, including butyrate, which is the main fuel for the colonic wall and has anticarcinogenic and anti-inflammatory properties. A good understanding of the growth requirements of butyrate-producing bacteria is important for the development of efficient strategies to promote these microbes in the gut, especially in cases where their abundance is altered. The demonstration of the inability of several dominant butyrate producers to grow in the absence of certain vitamins confirms the results of previous in silico analyses. Furthermore, establishing that strains prototrophic for thiamine or folate (butyrate producers and non-butyrate producers) were able to stimulate growth and affect the composition of auxotrophic synthetic communities suggests that the provision of prototrophic bacteria that are efficient cross feeders may stimulate butyrate-producing bacteria under certain in vivo conditions. We investigated the requirement of 15 human butyrate-producing gut bacterial strains for eight B vitamins and the proteinogenic amino acids by a combination of genome sequence analysis and in vitro growth experiments. The Ruminococcaceae species Faecalibacterium prausnitzii and Subdoligranulum variabile were auxotrophic for most of the vitamins and the amino acid tryptophan. Within the Lachnospiraceae , most species were prototrophic for all amino acids and several vitamins, but biotin auxotrophy was widespread. In addition, most of the strains belonging to Eubacterium rectale and Roseburia spp., but few of the other Lachnospiraceae strains, were auxotrophic for thiamine and folate. Synthetic coculture experiments of five thiamine or folate auxotrophic strains with different prototrophic bacteria in the absence and presence of different vitamin concentrations were carried out. This demonstrated that cross-feeding between bacteria does take place and revealed differences in cross-feeding efficiency between prototrophic strains. Vitamin-independent growth stimulation in coculture compared to monococulture was also observed, in particular for F. prausnitzii A2-165, suggesting that it benefits from the provision of other growth factors from community members. The presence of multiple vitamin auxotrophies in the most abundant butyrate-producing Firmicutes species found in the healthy human colon indicates that these bacteria depend upon vitamins supplied from the diet or via cross-feeding from other members of the microbial community. IMPORTANCE Microbes in the intestinal tract have a strong influence on human health. Their fermentation of dietary nondigestible carbohydrates leads to the formation of health-promoting short-chain fatty acids, including butyrate, which is the main fuel for the colonic wall and has anticarcinogenic and anti-inflammatory properties. A good understanding of the growth requirements of butyrate-producing bacteria is important for the development of efficient strategies to promote these microbes in the gut, especially in cases where their abundance is altered. The demonstration of the inability of several dominant butyrate producers to grow in the absence of certain vitamins confirms the results of previous in silico analyses. Furthermore, establishing that strains prototrophic for thiamine or folate (butyrate producers and non-butyrate producers) were able to stimulate growth and affect the composition of auxotrophic synthetic communities suggests that the provision of prototrophic bacteria that are efficient cross feeders may stimulate butyrate-producing bacteria under certain in vivo conditions.

Microbial communities frequently invade one another as a whole, a phenomenon known as community coalescence. Despite its potential importance for the assembly, dynamics, and stability of microbial consortia, as well as its prospective utility for microbiome engineering, our understanding of the processes that govern it is still very limited. Theory has suggested that microbial communities may exhibit cohesiveness in the face of invasions emerging from collective metabolic interactions across microbes and their environment. This cohesiveness may lead to correlated invasional outcomes, where the fate of a given taxon is determined by that of other members of its community—a hypothesis known as ecological coselection. Here, we have performed over 100 invasion and coalescence experiments with microbial communities of various origins assembled in two different synthetic environments. We show that the dominant members of the primary communities can recruit their rarer partners during coalescence (top-down coselection) and also be recruited by them (bottom-up coselection). With the aid of a consumer-resource model, we found that the emergence of top-down or bottom-up cohesiveness is modulated by the structure of the underlying cross-feeding networks that sustain the coalesced communities. The model also predicts that these two forms of ecological coselection cannot co-occur under our conditions, and we have experimentally confirmed that one can be strong only when the other is weak. Our results provide direct evidence that collective invasions can be expected to produce ecological coselection as a result of cross-feeding interactions at the community level.