Juan Francisco Martinez-Blanch

Background: Allergic rhinitis (AR) is an increasingly common chronic inflammatory condition of the nasal mucosa. While conventional anti‐allergy treatments are widely used, they can come with side effects and are not always effective. As a result, AR remains a significant concern for many millions of people worldwide, affecting quality of life and social functioning. Objective: To investigate clinical evidence for the role of probiotics and postbiotics in reducing AR symptoms. Methods: In this single‐centre, randomized, double‐blind, placebo‐controlled clinical trial, 72 adults aged 18–60 years with moderate–severe AR, taking first‐line medication, were studied. The primary outcome of the trial was to determine the effects of supplementation with the probiotic Bifidobacterium longum CECT 7347 (PRO) and the heat‐treated postbiotic of the same strain (POST) on symptoms associated with AR as assessed using the Combined Symptom and Medication Score (CSMS). The secondary outcomes of the study assessed the effects of the interventions over: quality of life (rhinitis quality of life questionnaire [RQLQ]), systemic immune response, local immune response, and faecal microbiota composition. Results: Statistically significant reduction in total CSMS after 8 weeks of supplementation was observed in the POST group compared to placebo control (CON) ( p = 0.022), showing on average a 0.6 greater reduction than placebo (CI: 0.09–1.12), equivalent to a 33.15% greater reduction and exceeding the World Allergy Organization's threshold for minimal clinically significant efficacy. Conclusion: POST intake for 8 weeks was associated with a statistically significant reduction of total CSMS compared to placebo. There was also improvement in RQLQ parameters when compared to baseline. PRO intake for 8 weeks resulted in non‐significant beneficial effects on AR‐related symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT05208528

Background: Subclinical psychological symptoms—such as low mood, perceived stress, and poor sleep—affect a large portion of the population and can impair quality of life despite remaining below clinical thresholds. The gut–brain axis has emerged as a promising target for interventions that support emotional and psychological resilience. Probiotics and postbiotics are gaining attention for their potential to modulate mood and stress via microbiome-related mechanisms, but human evidence remains limited, particularly in non-clinical populations. Objectives: We aimed to assess the effects of a two-strain combination of live microorganisms alongside a two-strain combination of heat-treated inactivated microorganisms on outcomes associated with anxiety, mood, perceived stress, and quality of life in healthy adults experiencing mild stress. Methods: This study was conducted in two parts. In Part I, a randomized, double-blind, placebo-controlled study, 100 participants were randomized to receive either a blend of live microorganisms (Bifidobacterium longum CECT 7347 and Lactobacillus rhamnosus CECT 8361) or an identical placebo once daily for 12 weeks. In Part II, a pilot feasibility study, a subset of eight placebo non-responders from Part I received the heat-inactivated preparation of the same bacterial strains in a 6-week trial extension phase. For Parts I and II, the primary outcome was the change in the Hamilton Anxiety Rating Scale (HAM-A). Secondary outcomes included measures of mood (Beck Depression Inventory (BDI); Patient Health Questionnaire-9 (PHQ-9)), stress (state and trait anxiety inventory (STAI); Perceived Stress Scale (PSS)), sleep (Pittsburgh Sleep Quality Index (PSQI)), quality of life (36-item Short Form Survey (SF-36)), gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale (GSRS)), salivary cortisol and microbiome modulation. Results: In Part I, there were no significant effects of the live blend on the HAM-A, indicating that the primary endpoint was not met. In addition, no significant effects were seen on the STAI or PSS scores when compared to the placebo. However, participants consuming the live blend trended toward a reduction in total PHQ-9 scores compared to placebo (p = 0.089), whilst preliminary exploratory analyses suggested an improvement in anhedonia (p = 0.045). Furthermore, there was a significant improvement in the vitality domain of the SF-36 compared to placebo (p = 0.017). On microbiome analysis, it was noted that consumption of the live blend was linked to the preservation of butyrate-producing bacteria, particularly members of the Pseudoflavonifractor genus and the Clostridium SGB6179 species. Furthermore, the abundance of B. longum species was found to be inversely associated with the total PSS Scores. In Part II, supplementation with the inactivated preparation resulted in significant within-group improvements for the vitality (p = 0.006) and social functioning (p = 0.010) domains of the SF-36 and improvements in PSS scores compared to baseline (p = 0.050). Conclusions: Supplementation with either the dual-strain live or inactivated formulations was associated with significant improvements in the vitality domain of the SF-36, whilst participants receiving the inactivated formulation demonstrated lower perceived stress and improved social functioning compared to baseline. Overall, the findings from this pilot study suggest that these two biotic consortia are well-tolerated and may be associated with improvements in measures of vitality in individuals with subclinical psychological symptoms. The subtle observations detected for stress and anhedonia suggest that further well-powered trials are needed to better characterize these findings, potentially in populations with greater baseline symptomatology.

Background: Constipation is a common gastrointestinal (GI) state for which probiotics have shown promise as a relief. This study examined the laxative effects of the strain Bifidobacterium animalis subsp. lactis CECT 8145 (BPL1^®) in a loperamide-induced rat model of constipation. Methods: Fifty-nine rats were divided into control and loperamide-induced constipation groups. Animals received a 3-day intervention with either placebo or probiotic BPL1^® at two doses: 1.5 × 10⁸ CFU (colony-forming units) (low) and 3 × 10⁹ CFU (high). The study assessed several parameters to determine the probiotic’s effect, including: stool and gut characteristics, gastrointestinal transit time (GTT), gene expression and gut microbiome composition. Results: While loperamide significantly decreased stool number, weight and humidity, BPL1^® supplementation effectively restored these parameters, being more pronounced at a high dose. Microbiome analysis showed that BPL1^® at a low dose reduced the abundance of Muribaculaceae and Muribaculum gordoncarteri, associated with constipation. In addition, Muribaculaceae abundance was negatively correlated with stool humidity. Functional microbiome profiling indicated that BPL1^® suppressed pathways related to mucin degradation, vancomycin resistance and isoleucine biosynthesis while promoting L-lactate and pyridoxal-P (vitamin B6) biosynthesis, which may support gut motility and barrier integrity. Conclusions:Bifidobacterium animalis subsp. lactis BPL1^® exhibits potential as a functional probiotic for relieving constipation through improving stool excretion and consistency, inducing taxonomic changes and beneficial functional modulation of the intestinal microbiome. These findings justify further investigation into the mechanisms of BPL1^® as a probiotic for constipation management.

Acute intermittent porphyria (AIP) is a genetic metabolic disorder characterized by neurovisceral attacks. Although high-carbohydrate diets or intravenous glucose administration can help alleviate incipient attacks in patients, these interventions may also promote insulin resistance and increase metabolic risk. This study explored targeted dietary interventions to manage hyperinsulinemia and to enhance glucose uptake in insulin-sensitive organs under high-carbohydrate diet. Body composition and fecal microbiota profile were also investigated in a murine model of the disease. Wild-type and AIP mice ( n = 6/group) were supplemented with tapioca maltodextrin in drinking water for 12 weeks, alongside heat-treated Bifidobacterium animalis subsp. lactis CECT-8145 (BPL1®HT), its by-product lipoteichoic acid (LTA), or the insulin-sensitizing agent α-lipoic acid (α-LA). Liver-targeted therapies, previously assessed in AIP mice, were also included in this study. AIP mice on a high-carbohydrate diet exhibited hyperinsulinemia and tissue-specific differences in glucose uptake compared to wild-type mice. Dysbiosis, marked by reduced fecal Dorea spp. and Adlercreutzia muris , alongside higher abundance of Escherichia coli, was also showed. Supplementation with α-LA and LTA revealed superior ability to improve glucose tolerance test and skeletal muscle glucose uptake, reduce hyperinsulinemia, and enhance body composition by increasing lean mass relative to fat, compared to gene therapy or liver-targeted insulin administration. Notably, LTA restored fecal microbiota profiles resembling those of wild-type mice. In conclusion, supplementation with LTA from BPL1®HT and α-LA may represent promising dietary interventions to manage glucose tolerance, improve insulin sensitivity in muscle and adipose tissues, and potentially ameliorate body composition in AIP patients under a high-carbohydrate diet.

Periodontal diseases are highly prevalent in dogs and intricately interconnected with the composition and functional attributes of the oral microbiota. The demand for non-invasive interventions to support oral health presents an opportunity for functional ingredients. The novel postbiotic heat-treated (HT) Lactiplantibacillus plantarum CECT 9161 inhibited growth and biofilm formation of oral microorganisms in vitro. The in vitro growth of saliva-derived biofilms was also inhibited and revealed microbiome modulation. Two doses of the postbiotic (LOW: 5 mg dog/day, HIGH: 25 mg/dog/day) were assessed in a placebo-controlled, double-blinded, 57-day clinical trial involving 60 dogs. Associations were found between the postbiotic, reduced plaque formation, and modulation of the oral microbiome, including increased abundance of genes involved in denitrification, heme and catechol biosynthesis, and oxidative stress reduction. The results suggest that HT Lactiplantibacillus plantarum CECT 9161 may support oral health in dogs by modifying the microbiome of supragingival plaque and reducing plaque formation.

Lacticaseibacillus paracasei is commonly isolated from dairy products and the microbiome of the human reproductive and gastrointestinal tract. We report the genome assembly of Lacticaseibacillus paracasei ORD 0998 (CECT 30660) with two contigs, having a size of 3,150,431 bp and a GC content of 46.33%.

Objectives: A randomised, double-blind, placebo-controlled pilot trial was conducted to assess the effect of heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in healthy adults with mild to moderate digestive symptoms. A total of 60 participants were recruited and received either HT-ES1 or an identical placebo for 8 weeks with a further follow-up at week 10. Methods: This study monitored changes in the total Gastrointestinal Symptom Rating Scale for IBS score (GSRS-IBS), Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS), IBS Quality of Life index (IBS-QoL), gut microbiome using 16S rRNA sequencing, and the Visceral Sensitivity Index, as well as a range of biochemical markers, anthropometric parameters, and adverse events. Results: While minimal changes were observed in gastrointestinal (GI) symptoms, the HT-ES1 group showed a significant decrease in total and non-HDL cholesterol compared to the placebo. The intervention group also exhibited a significant increase in the abundance of the genera Faecalibacterium and Anaerobutyricum, both of which were positively correlated with butyrate concentrations. Faecal calprotectin significantly increased over time in the placebo group but remained stable in the HT-ES1 group. Conclusions: Overall, these findings suggest that HT-ES1 may promote gut health by increasing butyrate-producing bacteria in the gut, maintaining normal levels of faecal calprotectin and reducing serum cholesterol.

Seven photosynthethic microbiomes were collected from field environmental samples to test their potential in polyhydroxybutirate (PHB) and exopolysaccharides (EPS) production, two alternatives to chemical-based polymers. Microscope observations together with microbial sequence analysis revealed the microbiome enrichment in cyanobacteria after culture growth under phosphorus limitation. PHB and EPS production were studied under three culture factors (phototrophy, mixotrophy and heterotrophy) by evaluating and optimizing the effect of three parameters (organic and inorganic carbon and days under light:dark cycles) by Box-Behnken design. Results showed that optimal conditions for both biopolymers synthesis were microbiome-dependent; however, the addition of organic carbon boosted PHB production in all the tested microbiomes, producing up to 14% _dcw PHB with the addition of 1.2 g acetate·L ^-1 and seven days under light:dark photoperiods. The highest EPS production was 59 mg·L ^-1 with the addition of 1.2 g acetate·L ^-1 and four days under light:dark photoperiods. The methodology used in this article is suitable for enriching microbiomes in cyanobacteria, and for testing the best conditions for bioproducts synthesis for further scale up.

The World Health Organization recommends exclusive breastfeeding on demand until at least the sixth month of life. Breast milk or infant formula is the infant’s primary food source until the age of one year, followed by the gradual introduction of other foods. During weaning, the intestinal microbiota evolves to a profile close to that of the adult, and its disruption can result in an increased incidence of acute infectious diseases. We aimed to determine whether a novel starting formula (INN) provides gut microbiota compositions more similar to those of breastfed (BF) infants from 6 to 12 months of age compared to a standard formula (STD). This study included 210 infants (70 per group) who completed the intervention until they reached the age of 12 months. In the intervention period, infants were divided into three groups. Group 1 received an INN formula with a lower protein content, a casein to whey protein ratio of approximately 70/30, twice as much docosahexaenoic acid as the STD formula, a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis, BPL1^TM HT), and twice as much arachidonic acid as the STD formula contained. The second group received the STD formula, while the third group was exclusively BF for exploratory purposes. In the course of the study, visits were conducted at 6 months and 12 months of age. Compared to the BF and STD groups, the Bacillota phylum levels in the INN group were significantly reduced after 6 months. At the end of 6 months, the alpha diversity indices of the BF and INN groups differed significantly from those of the STD group. At 12 months, the Verrucomicrobiota phylum levels in the STD group were significantly lower than those in the BF and INN groups. Based on the comparison between 6 and 12 months, the Bacteroidota phylum levels in the BF group were significantly higher than those in the INN and STD groups. When comparing the INN group with the BF and STD groups, Clostridium sensu stricto 1 was significantly higher in the INN group. The STD group had higher levels of calprotectin than the INN and BF groups at 6 months. The immunoglobulin A levels in the STD group were significantly lower than those in the INN and BF groups after 6 months. Both formulas had significantly higher levels of propionic acid than the BF group at 6 months. At 6 months, the STD group showed a higher quantification of all metabolic pathways than the BF group. The INN formula group exhibited similar behavior to the BF group, except for the superpathway of phospholipid biosynthesis (E. coli). We hypothesize that the novel INN formula may promote an intestinal microbiota that is more similar to the microbiota of an infant who consumes only human milk before the weaning period.

Exclusive breastfeeding is highly recommended for infants for at least the first six months of life. However, for some mothers, it may be difficult or even impossible to do so. This can lead to disturbances in the gut microbiota, which in turn may be related to a higher incidence of acute infectious diseases. Here, we aimed to evaluate whether a novel starting formula versus a standard formula provides a gut microbiota composition more similar to that of breastfed infants in the first 6 months of life. Two hundred and ten infants (70/group) were enrolled in the study and completed the intervention until 12 months of age. For the intervention period, infants were divided into three groups: Group 1 received formula 1 (INN) with a lower amount of protein, a proportion of casein to whey protein ratio of about 70/30 by increasing the content of α-lactalbumin, and with double the amount of docosahexaenoic acid/arachidonic acid than the standard formula; INN also contained a thermally inactivated postbiotic (Bifidobacterium animalis subsp. lactis). Group 2 received the standard formula (STD) and the third group was exclusively breastfed (BF) for exploratory analysis. During the study, visits were made at 21 days, 2, 4, and 6 months of age, with ±3 days for the visit at 21 days of age, ±1 week for the visit at 2 months, and ±2 weeks for the others. Here, we reveal how consuming the INN formula promotes a similar gut microbiota composition to those infants that were breastfed in terms of richness and diversity, genera, such as Bacteroides, Bifidobacterium, Clostridium, and Lactobacillus, and calprotectin and short-chain fatty acid levels at 21 days, 2 and 6 months. Furthermore, we observed that the major bacteria metabolic pathways were more alike between the INN formula and BF groups compared to the STD formula group. Therefore, we assume that consumption of the novel INN formula might improve gut microbiota composition, promoting a healthier intestinal microbiota more similar to that of an infant who receives exclusively human milk.