Effect of an α-Tocopherol-Containing Antioxidant Parenteral Emulsion upon Gut Microbiota in Preterm Infants

Preterm babies are born with an immature intestine and are at higher risk for intestinal failure and needing for parenteral nutrition than full-term newborns. These babies show an altered intestinal microbiota, which may results of key importance for later health. However, there is a lack of information on effect of parenteral formulas upon the establishing infant microbiota. Moreover, the microbiota alterations present in preterm newborns have been related with an altered redox-potential which hinders the establishment of strict anaerobes. Thus, interventions aimed at reducing the oxidative stress in these infants, including those under parenteral nutrition, could also affect the intestinal microbiota composition. We assessed the effect upon the gut microbiota of the administration during 30 days of a lipid emulsion, containing ω3 polyunsaturated fatty acids and α-tocopherol, or a control emulsion containing soybean-bases lipids to parenterally-fed preterm newborns. In spite of its high antioxidant potential, the infants receiving the experimental fat emulsion showed a trend to increase of facultative anaerobes such as enterobacteria and specifically of Klebsiella. This study stresses the need of further work monitoring the impact of early-life parenteral nutrition on the establishment of the intestinal microbiota

Evaluation of the ability of Bifidobacterium longum to metabolize human intestinal mucus

The ability of Bifidobacterium longum to use intestinal mucus as a metabolizable source was characterized. Bifidobacterium longum biotype longum NCIMB8809 was grown in a chemically semi-defined medium supplemented with human intestinal mucus, and the cytoplasmic protein profiles and several glycosyl hydrolase activities were analysed and compared with those obtained from the same bacterium grown in the absence of mucus. We were able to identify 22 different proteins in the cytoplasmic fraction, of which nine displayed a different concentration in the presence of mucus. Among the proteins whose concentrations varied, we found specific enzymes that are involved in the response to different environmental conditions, and also proteins that mediate interaction with mucus in bacteria. Significant changes in some glycoside-hydrolysing activities were also detected. In addition, stable isotope labelling of amino acids in cell culture demonstrated that B. longum incorporates leucine from the glycoprotein matrix of mucin within its proteins. This study provides the first proteomic data regarding the interaction of B. longum with intestinal mucus, and contributes to the understanding of the behaviour of this intestinal species in its natural ecological nich

Intestinal Immunomodulation and Shifts on the Gut Microbiota of BALB/c Mice Promoted by Two Bifidobacterium and Lactobacillus Strains Isolated from Human Samples

Bifidobacterium animalis subsp. lactis IPLA 20020 and Lactobacillus gasseri IPLA 20212, two strains isolated from human samples, were evaluated for safety and influence over the intestinal microbiota and cytokine production by the intestinal tissue of adult BALB/c mice. Mice were divided into four groups receiving during 8 days PBS or a suspension of each strain, prepared fresh or lyophilized (bifidobacteria), at an amount of 4x108 viable cells/day. This dose could be comparable to the probiotic intake of a human adult who consumed about 100-200 mL of functional fermented milk per day, considering the usual level of probiotics in commercial products. No microbial translocation to liver or alterations in food intake, weight, and behavior were observed in treated mice. Intestinal content of secretory immunoglobulin A (s-IgA) was not affected, discarding any adverse effect on the mucosa-associated immunity. The profile of intestinal proinflammatory/regulatory cytokines after intervention evidenced that the microbial strain administered and its cellular state (fresh or lyophilized) as well as the host tissue analyzed (small or large intestine) influenced the immune response and suggests a moderate shift towards a T helper 1 profile (Th1) in the large intestine after the administration of both strains. Changes on relative levels of some intestinal microbial groups were evidenced after intervention. It is noteworthy that butyrate was positively associated with a balanced pro-Th1 immune response. Therefore, B. animalis subsp. lactis IPLA20020 and L. gasseri IPLA 20212 could be considered potential probiotic candidates to be included in functional foods for balancing the intestinal immune response.Fil: Nogacka, Alicja M.. Instituto de Investigación Sanitaria del Principado de Asturias; España. Consejo Superior de Investigaciones Científicas. Instituto Superior de Productos Lácteos de Asturias; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Oddi, Sofia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Salazar, Nuria. Instituto de Investigación Sanitaria del Principado de Asturias; España. Consejo Superior de Investigaciones Científicas. Instituto Superior de Productos Lácteos de Asturias; EspañaFil: Reinheimer, Jorge Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: Gueimonde, Miguel. Instituto de Investigación Sanitaria del Principado de Asturias; España. Consejo Superior de Investigaciones Científicas. Instituto Superior de Productos Lácteos de Asturias; EspañaFil: Vinderola, Celso Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Lactología Industrial. Universidad Nacional del Litoral. Facultad de Ingeniería Química. Instituto de Lactología Industrial; ArgentinaFil: De Los Reyes Gavilán, Clara G.. Consejo Superior de Investigaciones Científicas. Instituto Superior de Productos Lácteos de Asturias; España. Instituto de Investigación Sanitaria del Principado de Asturias; Españ

Immunometabolic Profile Associated with Progressive Damage of the Intestinal Mucosa in Adults Screened for Colorectal Cancer: Association with Diet

Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC

Fecal Metabolome and Bacterial Composition in Severe Obesity:Impact of Diet and Bariatric Surgery

The aim of this study was to monitor the impact of a preoperative low-calorie diet and bariatric surgery on the bacterial gut microbiota composition and functionality in severe obesity and to compare sleeve gastrectomy (SG) versus Roux-en-Y gastric bypass (RYGB). The study also aimed to incorporate big data analysis for the omics results and machine learning by a Lasso-based analysis to detect the potential markers for excess weight loss. Forty patients who underwent bariatric surgery were recruited (14 underwent SG, and 26 underwent RYGB). Each participant contributed 4 fecal samples (baseline, post-diet, 1 month after surgery and 3 months after surgery). The bacterial composition was determined by 16S rDNA massive sequencing using MiSeq (Illumina). Metabolic signatures associated to fecal concentrations of short-chain fatty acids, amino acids, biogenic amines, gamma-aminobutyric acid and ammonium were determined by gas and liquid chromatography. Orange 3 software was employed to correlate the variables, and a Lasso analysis was employed to predict the weight loss at the baseline samples. A correlation between Bacillota (formerly Firmicutes) abundance and excess weight was observed only for the highest body mass indexes. The low-calorie diet had little impact on composition and targeted metabolic activity. RYGB had a deeper impact on bacterial composition and putrefactive metabolism than SG, although the excess weight loss was comparable in the two groups. Significantly higher ammonium concentrations were detected in the feces of the RYGB group. We detected individual signatures of composition and functionality, rather than a gut microbiota characteristic of severe obesity, with opposing tendencies for almost all measured variables in the two surgical approaches. The gut microbiota of the baseline samples was not useful for predicting excess weight loss after the bariatric process

Cambios en la microbiota intestinal y el metaboloma fecal en función del daño de la mucosa intestinal

Resumen del trabajo presentado a la 16ª Reunión de la Red Española de Bacterias Lácticas (RedBAL), celebrada en Madrid los días 11 y 12 de mayo de 2023.RTI2018-098288-B-I00, MCIN/AEI/10.13039/501100011033/FEDER, “Una manera de hacer Europa”; AYUD/2021/50981, Principado de Asturias; S.R.-S., contrato predoctoral Severo Ochoa (2021- BP20-012), Principado de Asturias; S.A., contrato postdoctoral del ISPA; N.S., contrato RYC2021-033521-I, MCIN/AEI/ 10.13039/501100011033 y European Union NextGenerationEU/PRTR.N

Resistant starch can improve insulin sensitivity independently of the gut microbiota

Background: Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS. To achieve this goal, we determined the effects of RS when added to a Western diet on host metabolism in mice with and without a microbiota. Results: RS feeding of conventionalized mice improved insulin sensitivity and redressed some of the Western diet-induced changes in microbiome composition. However, parallel experiments in germ-free littermates revealed that RS-mediated improvements in insulin levels also occurred in the absence of a microbiota. RS reduced gene expression of adipose tissue macrophage markers and altered cecal concentrations of several bile acids in both germ-free and conventionalized mice; these effects were strongly correlated with the metabolic benefits, providing a potential microbiota-independent mechanism to explain the physiological effects of RS. Conclusions: This study demonstrated that some metabolic benefits exerted by dietary RS, especially improvements in insulin levels, occur independently of the microbiota and could involve alterations in the bile acid cycle and adipose tissue immune modulation. This work also sets a precedent for future mechanistic studies aimed at establishing the causative role of the gut microbiota in mediating the benefits of bioactive compounds and functional foods

Poststroke Lung Infection by Opportunistic Commensal Bacteria Is Not Mediated by Their Expansion in the Gut Microbiota

Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection.Funded by Fundació la Marató de TV3 (ref. 201723-30-31-32) to Drs Planas, Urra, and Sancho; the Ministerio de Ciencia e Innovación (MICINN)/AEI/10.13039/501100011033 and European Regional Development Fund (ERDF) A way of making Europe by the European Union (PID2020-113202RB-I00 to Dr Planas); CSIC Interdisciplinary Thematic Platform Plataforma Temática Interdisciplinar (PTI)+Neuro-Aging of the Consejo Superior de Investigaciones Científicas (Dr Planas) funded M. Gallizioli. The work of Instituto de Productos Lácteos (IPLA)-Consejo Superior de Investigaciones Científicas (CSIC) group was partly financed by grant AYUD/2021/ 50981 from Principality of Asturias. The work of Institut de Química Avançada de Catalunya (IQAC)-CSIC was financed by Ministerio de Economía y Competitividad (AGL2017-83599-R) and MICINN (PID2020-117009RB-I00). Dr Díaz-Marugan was funded by La Caixa Foundation (ID 100010434; code LCF/BQ/DE16/11570021). Dr Arboleya received a postdoctoral Juan de la Cierva contract (MICINN, Ref. IJCI-2017-32156). Work in Dr Sancho laboratory was funded by Centro de Investigaciones Cardiovasculares (CNIC), European Union’s Horizon 2020 research and innovation program under grant agreement ERC-2016-Consolidator Grant 725091, and MICINN (PID2019-108157RB/AEI/10.13039/501100011033).Peer reviewe

Purification and Functional Characterization of a Novel α-l-Arabinofuranosidase from Bifidobacterium longum B667

The gene encoding a novel α-l-arabinofuranosidase from Bifidobacterium longum B667, abfB, was cloned and sequenced. The deduced protein had a molecular mass of about 61 kDa, and analysis of its amino acid sequence revealed significant homology and conservation of different catalytic residues with α-l-arabinofuranosidases belonging to family 51 of the glycoside hydrolases. Regions flanking the gene comprised two divergently transcribed open reading frames coding for hypothetical proteins involved in sugar metabolism. A histidine tag was introduced at the C terminus of AbfB, and the recombinant protein was overexpressed in Lactococcus lactis under control of the tightly regulated, nisin-inducible nisA promoter. The enzyme was purified by nickel affinity chromatography. The molecular mass of the native protein, as determined by gel filtration, was about 260 kDa, suggesting a homotetrameric structure. AbfB was active at a broad pH range (pH 4.5 to 7.5) and at a broad temperature range (20 to 70°C), and it had an optimum pH of 6.0 and an optimum temperature of 45°C. The enzyme seemed to be less thermostable than most previously described arabinofuranosidases and had a half-life of about 3 h at 55°C. Chelating and reducing agents did not have any effect on its activity, but the presence of Cu(2+), Hg(2+), and Zn(2+) markedly reduced enzymatic activity. The protein exhibited a high level of activity with p-nitrophenyl α-l-arabinofuranoside, with apparent K(m) and V(max) values of 0.295 mM and 417 U/mg, respectively. AbfB released l-arabinose from arabinan, arabinoxylan, arabinobiose, arabinotriose, arabinotetraose, and arabinopentaose. No endoarabinanase activity was detected. These findings suggest that AbfB is an exo-acting enzyme and may play a role, together with other glycosidases, in the degradation of l-arabinose-containing polysaccharides