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Lactate is formed by many species of colonic bacteria, and can accumulate to high levels in the colons of inflammatory bowel disease subjects. Conversely, in healthy colons lactate is metabolized by lactate-utilizing species to the short-chain fatty acids butyrate and propionate, which are beneficial for the host. Here, we investigated the impact of continuous lactate infusions (up to 20 mM) at two pH values (6.5 and 5.5) on human colonic microbiota responsiveness and metabolic outputs. At pH 5.5 in particular, lactate tended to accumulate in tandem with decreases in butyrate and propionate and with corresponding changes in microbial composition. Moreover, microbial communities with low numbers of lactate-utilizing bacteria were inherently less stable and therefore more prone to lactate-induced perturbations. These investigations provide clear evidence of the important role these lactate utilizers may play in health maintenance. These should therefore be considered as potential new therapeutic probiotics to combat microbiota perturbations. Lactate can be produced by many gut bacteria, but in adults its accumulation in the colon is often an indicator of microbiota perturbation. Using continuous culture anaerobic fermentor systems, we found that lactate concentrations remained low in communities of human colonic bacteria maintained at pH 6.5, even when dl -lactate was infused at 10 or 20 mM. In contrast, lower pH (5.5) led to periodic lactate accumulation following lactate infusion in three fecal microbial communities examined. Lactate accumulation was concomitant with greatly reduced butyrate and propionate production and major shifts in microbiota composition, with Bacteroidetes and anaerobic Firmicutes being replaced by Actinobacteria , lactobacilli, and Proteobacteria . Pure-culture experiments confirmed that Bacteroides and Firmicutes isolates were susceptible to growth inhibition by relevant concentrations of lactate and acetate, whereas the lactate-producer Bifidobacterium adolescentis was resistant. To investigate system behavior further, we used a mathematical model (microPop) based on 10 microbial functional groups. By incorporating differential growth inhibition, our model reproduced the chaotic behavior of the system, including the potential for lactate infusion both to promote and to rescue the perturbed system. The modeling revealed that system behavior is critically dependent on the proportion of the community able to convert lactate into butyrate or propionate. Communities with low numbers of lactate-utilizing bacteria are inherently less stable and more prone to lactate-induced perturbations. These findings can help us to understand the consequences of interindividual microbiota variation for dietary responses and microbiota changes associated with disease states. IMPORTANCE Lactate is formed by many species of colonic bacteria, and can accumulate to high levels in the colons of inflammatory bowel disease subjects. Conversely, in healthy colons lactate is metabolized by lactate-utilizing species to the short-chain fatty acids butyrate and propionate, which are beneficial for the host. Here, we investigated the impact of continuous lactate infusions (up to 20 mM) at two pH values (6.5 and 5.5) on human colonic microbiota responsiveness and metabolic outputs. At pH 5.5 in particular, lactate tended to accumulate in tandem with decreases in butyrate and propionate and with corresponding changes in microbial composition. Moreover, microbial communities with low numbers of lactate-utilizing bacteria were inherently less stable and therefore more prone to lactate-induced perturbations. These investigations provide clear evidence of the important role these lactate utilizers may play in health maintenance. These should therefore be considered as potential new therapeutic probiotics to combat microbiota perturbations.

Commensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. β-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of β-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here, we show that a dominant butyrate producer in the human gut, Faecalibacterium prausnitzii , is able to acquire and degrade various β-mannooligosaccharides (β-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two β-MOS utilization loci ( F. prausnitzii β-MOS utilization loci [ Fp MULs]) supported a concerted model whereby the imported β-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments of F. prausnitzii with the primary degraders Bacteroides ovatus and Roseburia intestinalis on polymeric β-mannan resulted in syntrophic growth, thus confirming the high efficiency of the Fp MULs’ uptake system. Genomic comparison with human F. prausnitzii strains and analyses of 2,441 public human metagenomes revealed that Fp MULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of β-mannan metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut. IMPORTANCE Commensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic, and detailed biochemical analyses, this work reveals the mechanism enabling F. prausnitzii , as a model Ruminococcaceae within Firmicutes , to cross-feed and access β-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows that Fp MULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of β-mannans/β-MOS as a common dietary component. Our findings provide a mechanistic understanding of the β-MOS utilization capability by F. prausnitzii that may be exploited to select dietary formulations specifically boosting this beneficial symbiont, and thus butyrate production, in the gut.

The human gut microbiota impacts on host health due to its ability to ferment non-digestible dietary substrates to produce mainly short chain fatty acids. Butyrate, specifically, plays a key role and is the major energy source for colonocytes. Investigations regarding the health effects exerted by the gut microbiota requires an excellent understanding of its composition which is dependent on both culturing and sequencing efforts. In this thesis, a previously uncultured bacterium from the Firmicutes phylum, proposed name Macfarlanella aminovorans, which belongs to a new genus and species was characterised. Both in vitro and in silico studies revealed that the bacterium uses few carbohydrates but can metabolise amino acids. In particular, M. aminovorans strain SS3/4 produced butyrate from glutamate via the 2-hydroxyglutarate pathway with butyryl-CoA: acetate CoA-transferase as the terminal enzyme. Secondly, the prebiotic potential of β-mannans derived from konjac, carob and spruce sources, was assessed using key representatives of the human gut microbiota. Carbohydrateactive enzyme profiles specific to β-mannan degradation complemented in vitro growth assays conducted with monocultures, bi-cultures and synthetic microbial consortia. The co-cultures provided insight into the cross-feeding interactions present between mannan degraders and non-degraders. Three out of the eight butyrate-producing Firmicutes (Roseburia intestinalis L1-82, Roseburia faecis M72/1 and Coprococcus eutactus ART55/1)tested were exceptional β-mannan degraders, suggesting the prebiotic potential of β-mannans. Lastly, genome-based analyses of a panel of gut anaerobes, including β-mannan degraders, were conducted to assess their suitability as candidate probiotics or biotherapeutics. Various traits, including virulence factors, antibiotic resistance genes, and ability to synthesise Bvitamins, were investigated. In particular, the butyrate producing strains R. faecis M72/1 and Faecalibacterium prausnitzii S3L/3 showed promise as next-generation probiotics and synbiotics. These studies contribute to enhancing our knowledge of the composition and metabolic capabilities of the human gut microbiota which will better inform efforts to promote health.

ABSTRACT β-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of β-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here we show that a dominant butyrate-producer in the human gut, Faecalibacterium prausnitzii, is able to acquire and degrade various β-mannooligosaccharides (β-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two β-mannooligosaccharides (β-MOS) utilization loci (FpMULs) supported a concerted model whereby the imported β-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments of F. prausnitzii with the primary degrader Bacteroides ovatus on polymeric β-mannan resulted in syntrophic growth and production of butyrate, thus confirming the high efficiency of the FpMULs’ uptake system. Genomic comparison with human F. prausnitzii strains and analyses of 2441 public human metagenomes revealed that FpMULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of β-mannans metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut. Importance Commensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic and detailed biochemical analyses this work reveals the mechanism enabling F. prausnitzii, as a model clostridial cluster IV Firmicute, to cross-feed and access β-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows that FpMULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of β-mannans/β-MOS as a common dietary component. Our findings provide a mechanistic understanding of the β-MOS utilization capability by F. prausnitzii that may be exploited to select dietary formulations specifically boosting this beneficial symbiont, thus butyrate production, in the gut.

La protección del origen geográfico de los productos ha adquirido una relevancia creciente en las últimas décadas, impulsada tanto por las transformaciones del mercado como por la evolución de las expectativas del consumidor, superándose progresivamente la regulación fragmentada de esta materia. Frente a la estandarización de la oferta global, los productos vinculados a un territorio representan no solo una garantía de autenticidad y calidad diferenciada, sino también una expresión de identidad cultural y de compromiso con el entorno. En este contexto, la sostenibilidad emerge como una dimensión que trasciende el aspecto comercial para conectar el origen geográfico con modelos de producción sostenibles en términos ambientales, sociales y económicos. La Unión Europea ha incorporado progresivamente esta perspectiva al régimen jurídico de las denominaciones de origen y las indicaciones geográficas protegidas, reforzando su papel como herramientas de cohesión territorial y transición ecológica. El Reglamento 2024/1143 relativo a las indicaciones geográficas para vinos, bebidas espirituosas y productos agrícolas, reconoce explícitamente esta función, permitiendo que los pliegos de condiciones integren prácticas sostenibles de manera verificable. Esta evolución normativa no solo responde a exigencias del mercado, sino también a una visión más amplia de desarrollo territorial. En este trabajo se analiza dicho proceso y se examina el caso de la provincia de Alicante como ejemplo paradigmático de anticipación a los estándares actuales en materia de sostenibilidad y origen geográfico.

La casa en Laeso de Per Kirkeby (1938-2018) es una obra que deviene de la memoria material del propio lugar. El proyecto consiste en la configuración de una arquitectura cerámica ejecutada a partir de arcilla de la propia isla, que une pasado y presente por medio de la materia. La obra es directa y honesta en el uso del ladrillo, permitiéndonos una experiencia material completa. Este trabajo de investigación profundiza en el estudio de este proyecto en relación con la memoria física del emplazamiento, mediante un diálogo directo con la geología. Para el desarrollo del texto, se vinculará la forma básica der Erdaufwurf descrita en los escritos fundamentales de Gottfried Semper (1851), así como la relación existente entre materia y memoria expuesta por Henri Bergson (1896).

El presente trabajo pretende indagar en el punto de vista que el escritor dieciochesco Vaca de Guzmán tenía sobre la pena de muerte. Para ello hemos utilizado como fuente principal su Suplemento al Enrique Wanton, la continuación de una novela italiana en la que vertía diferentes opiniones Nos hemos detenido en un pasaje relativo a la pena de muerte y hemos comparado lo ahí expuesto con la filosofía de la época. Tras esto hemos podido determinar que Vaca de Guzmán fue un pensador reaccionario cercano a Hobbes que apoyaba la pena capital en contra de autores como Beccaria o Jovellanos.

La remodelación de la autopista M-30, tunelizando su trazado a lo largo del río Manzanares, ha permitido crear una nueva zona verde sobre los terrenos liberados del tráfico: Madrid Río. Tras su inauguración en 2011, la denuncia sobre los posibles efectos gentrificadores sobre los barrios adyacentes ha sido recurrente. El artículo pretende mostrar si la producción de renta urbana diferencial propiciada por la mejora ambiental ha generado un proceso de renovación-sustitución de la población residente. Para ello se aborda el análisis de los cambios socio-demográficos y de la evolución del nivel de renta experimentado en su entorno más próximo a nivel de sección censal. Los resultados demuestran que los cambios están estrechamente vinculados con las características del tejido residencial preexistente, respondiendo a procesos urbanos más amplios (renovación de antiguas zonas industriales, incremento de la multiculturalidad en relación con la reciente oleada inmigratoria) más que a efectos directamente atribuibles a la operación. Frente a la generalizada interpretación de estos procesos bajo la narrativa de la gentrificación, la importancia de la geografía del parque residencial (expresada en términos de localización y atributos físicos y sociales) es determinante para encontrar argumentos explicativos al proceso de selección socio-demográfica.

The house in Laso by Per Kirkeby (1938-2018) is a work that springs from the material memory of the place itself. The design comprises an arrangement of architecture in earthenware made from clay from the island itself, uniting past and present through matter. The work is direct and honest in its use of brick, affording us a complete material experience. This study examines the project in depth in relation to the physical memory of the site in a direct dialogue with geology. The text’s line of argument will refer to the basic form of the Erdaufwurf or “earthworks” described in the seminal writings of Gottfried Semper (1851), as well as the relationship between matter and memory proposed by Henri Bergson (1896). La casa en Læsø de Per Kirkeby (1938 - 2018) es una obra que deviene de la memoria material del propio lugar. El proyecto consiste en la configuración de una arquitectura cerámica ejecutada a partir de arcilla de la propia isla, que une pasado y presente por medio de la materia. La obra es directa y honesta en el uso del ladrillo, permitiéndonos una experiencia material completa. Este trabajo de investigación profundiza en el estudio de este proyecto en relación con la memoria física del emplazamiento, mediante un diálogo directo con la geología. Para el desarrollo del texto, se vinculará la forma básica der Erdaufwurf descrita en los escritos fundamentales de Gottfried Semper (1851), así como la relación existente entre materia y memoria expuesta por Henri Bergson (1896).