Hematopoietic stem cell transplantation (HSCT) offers curative potential for hematologic malignancies and immune disorders, yet pulmonary complications remain major contributors to non-relapse morbidity and mortality. Traditionally attributed to immune suppression and graft-versus-host disease (GvHD), these complications are increasingly recognized to involve disruption of pulmonary microbial communities. A growing body of clinical and experimental evidence indicates that HSCT-associated perturbations in the lung microbiome, driven by conditioning, antimicrobials, immune injury, and infection, are associated with distinct post-transplant pulmonary phenotypes and, in some cohorts, with mortality risk. Whether these microbial shifts represent causal contributors to lung injury or contextual biomarkers of immune vulnerability remains unresolved, and this distinction carries direct implications for microbiome-targeted intervention. Dysbiotic shifts in the lung have been associated with both infectious and non-infectious complications, including idiopathic pneumonia syndrome, bronchiolitis obliterans syndrome, and fibrotic lung disease. Gut-lung microbial crosstalk may amplify or reflect systemic immune dysfunction, though the directionality of this relationship remains incompletely characterized. Multi-omics approaches, integrating metagenomics, metatranscriptomics, and metabolomics, are beginning to define the host-microbiome interaction signatures that distinguish injury subtypes and predict outcomes. This review synthesizes mechanistic insights into lung microbiome-immune interactions after HSCT, critically appraises the methodological constraints on the current evidence base, and evaluates microbiome-based interventions, including fecal microbiota transplantation, inhaled postbiotics, and precision antimicrobials, as candidate strategies for respiratory protection in transplant recipients, while acknowledging that prospective interventional evidence in this population remains limited.

BACKGROUND:Gut microbiota and their metabolites play a key role in digestive dysimmunity and tolerance breakdown, leading to pathologies such as food protein-induced enterocolitis syndrome (FPIES). This study aimed to compare both the gut and salivary microbiota over time between the allergic and tolerant patients and the matched controls. METHODS:Faecal and salivary samples were collected longitudinally from FPIES allergic patients on an elimination diet, and after their natural tolerance acquisition, and from matched controls (1:1 ratio). 16S rRNA gene sequencing and biostatistical analyses (ALDEx2, ANCOM-BC, DESeq2, LEfSe, and MaAsLIN2) were used to compare microbiota composition between groups. The measurement of faecal short-chain fatty acids (SCFAs) using gas chromatography evaluated the gut microbiota functions. RESULTS:Thirty-eight allergic patients were included (median age: 1.3 years), and 22 became tolerant over time. Allergic patients exhibited lower gut and salivary alpha-diversities, and several different genera (12 in stools, including less Ruminococcus, and 2 in saliva), and higher relative abundance of acetate than the controls. With tolerance acquisition, faecal alpha-diversities partially increased, whereas SCFAs normalised. Ultimately, there were more differences in faecal and salivary microbiota in allergic patients versus after tolerance acquisition (i.e., more Blautia, Ruminococcus, Faecalibacterium, Prevotella-9, and less Escherichia-Shigella in tolerant patients) than between the controls over time. CONCLUSION:The faecal and salivary dysbiosis observed in allergic patients with FPIES partially resolved after tolerance acquisition. Understanding the underlying mechanisms of dysbiosis is crucial to prevent and help manage FPIES. A prolonged follow-up could determine whether dysbiosis resolution may be complete, and whether this early infancy dysbiosis has long-term consequences on health.

Microplastic pollution is a growing global concern, yet the human health effects of exposure to microplastics, particularly in interaction with dietary factors, are not well understood. In this study, we investigated the impact of polyethylene microplastics (PE-MPs) on intestinal homeostasis in mice fed either a normal (ND) or Western (WD) diet for 90 days. Mice were orally exposed to PE-MPs (10 mg/kg body weight/day) throughout the experimental period. Under ND conditions, PE-MP exposure induced subtle changes in gut microbiota composition and short-chain fatty acid (SCFA) production, including a significant decrease in propionate, without overt intestinal inflammation. In contrast, under WD conditions, PE-MP exposure markedly exacerbated the diet-induced phenotype. WD-fed mice exposed to PE-MPs exhibited increased body weight gain, decreased expression of tight-junction related-genes and elevated faecal levels of the inflammatory marker lipocalin-2 and secretory IgA. These effects were accompanied by decreased abundances of Akkermansiaceae and Saccharimonadaceae, enrichment of Peptostreptococcaceae, and reduced caecal levels of propionate, isobutyrate, isovalerate and caproate. Together, these findings indicate that PE-MP exposure exacerbates WD effects, resulting in altered gut microbiota composition and metabolic activity, and increased intestinal inflammation. This study emphasises the importance of taking nutritional status into account when evaluating the toxicity of MPs and sheds new light on how this emerging class of food contaminant interacts with dietary stressors to shape host-microbiome relationships.

Severe asthma (SA) is a heterogeneous condition characterized by multiple phenotypes, each characterized by different endotypes. Understanding the mechanisms occurring in the lungs of children with SA can help in understanding pathogenesis and in providing the most effective therapeutic strategies. This article describes microbiota, metabolites, and soluble immune components assessed in bronchoalveolar lavage (BAL) fluids from children with severe asthma (n = 20) and age-matched disease controls (n = 10). The article includes: (i) the protocol used to process BAL samples for 16S rRNA gene amplicon sequencing, metabolomic profiling and immune components assays; (ii) the bioinformatics steps applied to 16S rRNA and metabolomics dataset; (iii) an overview of the raw 16S rRNA gene amplicon sequencing data, presented as ASV and affiliation tables, raw data from untargeted metabolomics and the abundances of each of the eighty eight metabolites annotated with the highest confidence level, and concentrations of seventy three cytokines and of total IgG, IgA and IgE. Each dataset is available in the INRAE data repository (https://entrepot.recherche.data.gouv.fr/dataverse/inrae) with respective DOI: MICROBIOTA: 10.57745/LL3TFW, METABOLITES: 10.57745/1L8VRI, IMMUNE COMPONENTS: 10.57745/JOOGRQThese datasets provide valuable resources for further investigating the molecular mechanisms underlying severe asthma in children and its trajectories. They also offer the potential to identify a local signature of severe asthma through complementary multi-omics analyses and to discover local biomarkers associated with asthma endotypes. Datasets can also be reused to compare with other cohorts (children or adults) or to serve as reference datasets for other pulmonary diseases.

Neutropenic enterocolitis (NE) is a severe digestive complication of chemotherapy, primarily affecting patients with acute myeloid leukemia (AML). We hypothesized that NE is linked to intestinal barrier dysfunction and gut dysbiosis. Sixty-five AML patients undergoing induction chemotherapy were included in this prospective monocentric cohort. Among them, 26 patients (40%) were diagnosed with NE. Stool samples were subjected to bacterial load quantification (all bacteria quantitative PCR), 16s rRNA metagenomic analysis, and short-chain-fatty-acids quantification. Additionally, fecal calprotectin and human 𝛃-defensin 2 along with plasmatic inflammatory cytokines, and citrulline levels were measured. Human transcriptomic analysis was conducted on samples obtained from anatomical specimens of colectomies of NE patients. Gut microbiota underwent significant alterations after chemotherapy, transitioning from a diverse and balanced enterotype to enterotypes exhibiting a reduced α-diversity, an increased abundance of Enterococcus faecalis, and a decreased abundance of butyrate-producing genera, which correlated with a decreased fecal concentration of butyrate. Simultaneously, post-chemotherapy, plasma citrulline concentrations decreased indicating enterocyte damages. Finally, human transcriptomic analysis found a significant upregulation of the JAK-STAT signaling KEGG pathway in the colons of NE patients encompassing cytokines (IL-6, OSM-OSMR) that play a pivotal role in sustaining local inflammation within the digestive tract. This work reaffirms the significant influence of chemotherapy on the gut microbiota and the integrity of the enterocyte barrier. Severe NE is marked by the development of a local inflammatory response that may be induced by the reduction in butyrate levels. The study was registered on Clinicaltrials.gov (identifier: NCT04438278).

The lung mucosa at birth and shortly after is particularly vulnerable to respiratory syncytial virus (RSV) infection. Respiratory disease severity is strongly influenced by the age at first exposure, which may also affect the trajectory of airway function. Early-life represents a critical window for lung development and initial microbiota colonization, both of which shape mucosal immune responses to RSV. The impact of the initial establishment of the lung microbiota by its primo-colonizing strains on susceptibility to RSV infection in neonatal mice remains poorly described. In the present study, we showed that early-life primo-colonizing bacterial strains in the mouse lung differentially induce innate immune responses and influence RSV susceptibility in ex vivo models using lung explants and alveolar macrophages (AMs). We identified a specific bacterial strain (strain 17) whose prior exposure enhances type I interferon (IFN-I) responses in AMs upon RSV infection and reduces viral replication both ex vivo and in vivo in lung tissues. Intranasal administration of this strain during early life prevented the development of immunopathological responses upon RSV reinfection in adult mice. Finally, using a translational human airway epithelium model, we demonstrated that pre-exposure to strain 17 restricts RSV spread without cytotoxicity, likely via enhanced β-defensin 2 production. These findings highlight the potential of early-life microbiota modulation as a promising intervention for preventing RSV disease and its long-term respiratory consequences.

This document presents the opinion of the French Agency for Food, Environmental and Occupational Health & Safety (ANSES), established from the work of its Working Group on “Risks associated with the consumption of Nitrites and Nitrates" (NiNa WG) and validated by its Expert Committees on “Assessment of the biological risks in foods” (CES BIORISK) and “Assessment of physico-chemical risks in food” (CES ERCA). Following a request from the Directorate General for Health, the Directorate General for Food and the Directorate General for Competition, Consumer Affairs and Fraud Control, ANSES was asked to deliver an opinion on the risks linked to nitrites and nitrates. Specifically, ANSES provided a scientific assessment associated with the following work themes regarding questions of (i) the impact of reducing nitrite/nitrate levels in foodstuffs on the fate of pathogenic bacteria in certain foods, (ii) the assessment of overall exposure to nitrates and nitrites from all sources in France and the proposal of actions that could help reduce this exposure, (iii) evaluating if new scientific knowledge could justify revisiting EFSA's ADIs/Health-Based Guidance Values (HBGVs) for nitrates and nitrites, and (iv) better characterizing their link to human cancer risk from meat product consumption. The opinion first presents the substances of interest, their origin and the regulatory framework. Then this opinion sets out the conclusions of the microbiological risk for three foodborne pathogens associated with reducing nitrate/nitrite levels as additives in three types of cured meats. This is followed by a presentation of the conclusions relating to the assessment of the available epidemiological and toxicological data in the light of recent scientific data. Finally, this enables the characterization of the risk associated with ingested nitrates and nitrites after exposure has been estimated. The opinion provides recommendations to continue epidemiological studies to confirm or refute suspected relationships for certain cancers and to conduct experimental studies for the establishment of ADIs considering the combined exposure to nitrates, nitrites and nitroso compounds. Furthermore, reducing the population's exposure to nitrites and nitrates involves collective and individual measures. As part of collective measures, in addition to controlling the quality of water intended for human consumption, a relevant measure would be to reduce the use of nitrites in processed meat products while implementing strict compensatory measures to address microbiological risk. This opinion finally emphasizes the importance of individual measures, by adhering to recommendations for processed meat consumption, limiting it to 150g/week, and diversifying the consumption of fruits and vegetables.

Faecalibacterium has recently garnered attention for its potential health implications. To better understand its role, we developed and assessed real-time PCR assays for detecting and quantifying various Faecalibacterium species in human stool samples from both healthy individuals and Crohn's disease patients, either in flare or remission. The assays targeted the Microbial Anti-inflammatory Molecule (MAM) genes, which encode MAM proteins. These assays demonstrated 100% species-specificity using strains from six Faecalibacterium species: Faecalibacterium prausnitzii, Faecalibacterium taiwanense, Faecalibacterium duncaniae, Faecalibacterium longum, Faecalibacterium hattori, and Faecalibacterium CNCM4541. They also showed high sensitivity with detection limits of 10^5 bacteria per gram of sample. In healthy individuals, the different Faecalibacterium species varied in abundance. F. taiwanense, F. duncaniae, and F. longum were the most prevalent, around 10^10 bacteria/g of stool. In contrast, F. hattori and CNCM4541 were less abundant, with 10^7 bacteria/g. Despite its low abundance, F. hattori was present in all healthy subjects, while CNCM4541 was detected in only 50% of them. Notably, F. taiwanense, F. duncaniae, and F. longum were found in all healthy individuals. In Crohn's disease patients, both in flare and remission, a decrease in Faecalibacterium species was observed, with no recovery in remission. The most abundant species in Crohn's disease patients were F. prausnitzii and F. duncaniae, around 10^7 bacteria/g, while F. longum, F. hattori, and F. taiwanense were present at lower levels (10^6 bacteria/g), and CNCM4541 was no longer detected. Interestingly, F. prausnitzii showed a smaller decrease in abundance compared with other species. Moreover, F. prausnitzii was significantly more prevalent in patients in remission than in those in flare, suggesting that it may be more resistant to inflammation. These findings highlight the importance of accurately characterizing and quantifying Faecalibacterium species to better understand their role in health and disease.

Severe asthma (SA) is a heterogeneous condition characterized by multiple phenotypes, each characterized by different endotypes. Understanding the mechanisms occurring in the lungs of children with SA can help in understanding pathogenesis and in providing the most effective therapeutic strategies. This article describes microbiota, metabolites, and soluble immune components assessed in bronchoalveolar lavage (BAL) fluids from children with severe asthma (n = 20) and age-matched disease controls (n = 10). The article includes: (i) the protocol used to process BAL samples for 16S rRNA gene amplicon sequencing, metabolomic profiling and immune components assays; (ii) the bioinformatics steps applied to 16S rRNA and metabolomics dataset; (iii) an overview of the raw 16S rRNA gene amplicon sequencing data, presented as ASV and affiliation tables, raw data from untargeted metabolomics and the abundances of each of the eighty eight metabolites annotated with the highest confidence level, and concentrations of seventy three cytokines and of total IgG, IgA and IgE. Each dataset is available in the INRAE data repository (https://entrepot.recherche.data.gouv.fr/dataverse/inrae) with respective DOI: MICROBIOTA: 10.57745/LL3TFW, METABOLITES: 10.57745/1L8VRI, IMMUNE COMPONENTS: 10.57745/JOOGRQ These datasets provide valuable resources for further investigating the molecular mechanisms underlying severe asthma in children and its trajectories. They also offer the potential to identify a local signature of severe asthma through complementary multi-omics analyses and to discover local biomarkers associated with asthma endotypes. Datasets can also be reused to compare with other cohorts (children or adults) or to serve as reference datasets for other pulmonary diseases.

The lung mucosa at birth and shortly after is particularly vulnerable to respiratory syncytial virus (RSV) infection. Respiratory disease severity is strongly influenced by the age at first exposure, which may also affect the trajectory of airway function. Early-life represents a critical window for lung development and initial microbiota colonization, both of which shape mucosal immune responses to RSV. The impact of the initial establishment of the lung microbiota by its primo-colonizing strains on susceptibility to RSV infection remains largely unknown. In the present study, we showed that early-life primo-colonizing bacterial strains in the mouse lung differentially induce innate immune responses and influence RSV susceptibility in ex vivo models using lung explants and alveolar macrophages. We identified a specific bacterial strain that enhances IFN-I antiviral pathways and reduces RSV replication both in vitro and in vivo. Intranasal administration of this strain to neonatal mice prevented the development of immunopathological responses upon RSV reinfection in adulthood. These findings highlight the potential of early-life microbiota modulation as a promising intervention for preventing RSV disease and its long-term respiratory consequences. ### Competing Interest Statement The authors have declared no competing interest. Air Liquide (France), https://ror.org/0431b2v07 Vaincre la Mucoviscidose, https://ror.org/00gp9bw49 Association Gregory Lemarchal, Région Ile de France - DIM Agence Nationale de la Recherche, https://ror.org/00rbzpz17, ANR-13-BSV3-0016, ANR-24-NEOMIS

Intestinal epithelium renewal strictly depends on fine regulation between cell proliferation, differentiation, and apoptosis. While murine intestinal microbiota has been shown to modify some epithelial cell kinetics parameters, less is known about the role of the human intestinal microbiota. Here, we investigated the rate of intestinal cell proliferation in C3H/HeN germ-free mice associated with human flora (HFA, n = 8), and in germ-free (n = 15) and holoxenic mice (n = 16). One hour before sacrifice, all mice were intraperitoneally inoculated with 5-bromodeoxyuridine (BrdU), and the number of BrdU-positive cells/total cells (labelling index, LI), both in the jejunum and the colon, was evaluated by immunohistochemistry. Samples were also observed by scanning electron microscopy (SEM). Moreover, the microbiota composition in the large bowel of the HFA mice was compared to that of of human donor’s fecal sample. No differences in LI were found in the small bowels of the HFA, holoxenic, and germ-free mice. Conversely, the LI in the large bowel of the HFA mice was significantly higher than that in the germ-free and holoxenic counterparts (p = 0.017 and p = 0.048, respectively). In the holoxenic and HFA mice, the SEM analysis disclosed different types of bacteria in close contact with the intestinal epithelium. Finally, the colonic microbiota composition of the HFA mice widely overlapped with that of the human donor in terms of dominant populations, although Bifidobacteria and Lactobacilli disappeared. Despite the small sample size analyzed in this study, these preliminary findings suggest that human intestinal microbiota may promote a high proliferation rate of colonic mucosa. In light of the well-known role of uncontrolled proliferation in colorectal carcinogenesis, these results may deserve further investigation in a larger population study.

The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2 alpha. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced alpha-diversity of microbiota, and led to Lactobacillaceae becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of Bifidobacterium longum.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Introduction: A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity, and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods: Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no-mutation group). Results: After a median (P10; P90) duration of 5.4 (2.2; 10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of -1.7 (-3.1; -0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype, and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (beta = 0.90, p < 0.001), mid-parental height SDS (beta = 0.27; p = 0.005), birth weight SDS (beta = 0.15; p = 0.051), age at start (beta = 0.07; p = 0.032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p < 0.001) from -1.0 (-2.5; 0.0) at start to -0.2 (-1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion: Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.

The promising next-generation probiotic Faecalibacterium prausnitzii is one of the most abundant acetate-consuming, butyrate-producing bacteria in the healthy human gut. Yet, little is known about how acetate availability affects this bacterium’s gene expression strategies. Here, we investigated the effect of acetate on temporal changes in the transcriptome of F. duncaniae A2-165 cultures using RNA sequencing. We compared gene expression patterns between two growth phases (early stationary vs. late exponential) and two acetate levels (low: 3 mM vs. high: 23 mM). Only in low-acetate conditions, a general stress response was activated. In high-acetate conditions, there was greater expression of genes related to butyrate synthesis and to the importation of B vitamins and iron. Specifically, expression was strongly activated in the case of the feoAABC operon, which encodes a FeoB ferrous iron transporter, but not in the case of the feoAB gene, which encodes a second putative FeoAB transporter. Moreover, excess ferrous iron repressed feoB expression but not feoAB. Lastly, FeoB but not FeoAB peptides from strain A2-165 were found in abundance in a healthy human fecal metaproteome. In conclusion, we characterized two early-stationary transcriptomes based on acetate consumption and this work highlights the regulation of feoB expression in F. duncaniae A2-165.

Therapeutic antibodies (Ab) have revolutionized the management of multiple illnesses including respiratory tract infections (RTIs). However, anti-infectious Ab displayed several limitations including antigen restrictiveness, narrowed therapeutic windows, and limited dose in the vicinity of the target when delivered by parenteral routes. Strategies enhancing further Ab-dependent containment of infection are currently needed. Here we showed that a combination of inhaled anti-infectious Ab and probiotics is an efficient formulation to protect against lung infection. Using a mouse model of Pseudomonas aeruginosa-induced pneumonia, we demonstrated a synergistic effect reducing both bacterial burden and pro-inflammatory response affording protection against primary and secondary infections. This is the first study showing that the local combination in the airways of anti-infective Ab and probiotics subverts suboptimal potency of Ab monotherapy and provides protection against respiratory pathogen.

ABSTRACT Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a “good” donor as well as the intrinsic variability of donor-derived products’ taxonomic composition limits the translatability and reproducibility of these studies. Thus, the pooling of donors’ feces has been proposed to homogenize product composition and achieve higher taxonomic richness and diversity. In this study, we compared the metagenomic profile of pooled products to corresponding single donor-derived products. We demonstrated that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria known to produce anti-inflammatory short chain fatty acids compared to single donor-derived products. We then evaluated pooled products’ efficacy compared to corresponding single donor-derived products in Salmonella and C. difficile infectious mouse models. We were able to demonstrate that pooled products decreased pathogenicity by inducing a structural change in the intestinal microbiota composition. Single donor-derived product efficacy was variable, with some products failing to control disease progression. We further performed in vitro growth inhibition assays of two extremely drug-resistant bacteria, Enterococcus faecium vanA and Klebsiella pneumoniae oxa48, supporting the use of pooled microbiotherapies. Altogether, these results demonstrate that the heterogeneity of donor-derived products is corrected by pooled fecal microbiotherapies in several infectious preclinical models. IMPORTANCE Growing evidence demonstrates the key role of the gut microbiota in human health and disease. Recent Food and Drug Administration approval of fecal microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on their potential to treat pathological conditions associated with gut dysbiosis. In this study, we combined metagenomic analysis with in vitro and in vivo studies to compare the efficacy of pooled microbiotherapy products to corresponding single donor-derived products. We demonstrate that pooled products are more homogeneous, diverse, and enriched in beneficial bacteria compared to single donor-derived products. We further reveal that pooled products decreased Salmonella and Clostridioides difficile pathogenicity in mice, while single donor-derived product efficacy was variable, with some products failing to control disease progression. Altogether, these findings support the development of pooled microbiotherapies to overcome donor-dependent treatment efficacy.