Actinomycetota

What was studied?

This study examined the fecal microbiome of children newly diagnosed with Crohn's disease (CD) before any treatment was started. The researchers compared microbial composition between these CD patients and children with functional gastrointestinal disorders. They also looked at whether specific microbial patterns correlated with the severity of CD, as measured by the Pediatric Crohn's Disease Activity Index (PCDAI).

Who was studied?

The cohort included 43 newly diagnosed, treatment-naive pediatric CD patients. They were compared against 139 age- and sex-matched controls who had other functional gastrointestinal disorders rather than CD. All participants were pediatric patients, and the comparison group was matched specifically to isolate microbial differences attributable to CD rather than age or sex.

What were the most important findings?

Microbial richness and diversity were significantly lower in children with CD compared to controls. Taxonomic analysis showed enrichment of pro-inflammatory bacteria, specifically Fusobacteria and Proteobacteria, alongside depletion of favorable taxa, Firmicutes and Verrucomicrobia. Higher PCDAI scores (indicating greater disease activity) were linked to enrichment of pro-inflammatory genera, Hungatella and Veillonella, and depletion of protective Lachnospiraceae.

What are the greatest implications of this study?

The findings support fecal microbiome profiling as a potential tool for distinguishing CD from other functional gastrointestinal disorders in children at diagnosis. The correlation between specific microbial shifts and disease activity suggests the microbiome could help track or predict clinical course. This could ultimately aid clinicians in making more informed treatment decisions for a disease whose course is otherwise unpredictable.

What was studied?

This study characterized the gut microbiome in the context of HTLV-1 infection and its clinical stages, including the neuroinflammatory disease HAM/TSP. Researchers analyzed fecal bacterial composition and diversity using Illumina MiSeq sequencing, drawing an analogy to the established gut-brain axis role seen in other neurological diseases like multiple sclerosis. Functional analysis was also performed to identify differentially enriched gene categories and KEGG metabolic modules. The overall aim was to determine whether gut microbiome alterations track with HTLV-1 infection and disease progression to HAM/TSP.

Who was studied?

The study included 112 Brazilian individuals in a cross-sectional design. This comprised 24 healthy controls and 88 HTLV-1-infected individuals, the latter group spanning different disease stages: 38 patients with HAM, 17 with intermediate syndromes, and 33 asymptomatic carriers. Fecal samples were collected from each participant for sequencing and functional analysis.

What were the most important findings?

HTLV-1-infected individuals showed significant gut dysbiosis compared to healthy controls, marked by reduced bacterial diversity and an inverted Firmicutes/Bacteroidetes ratio. Specific bacterial genera changed across disease stages, and functional KEGG modules were differentially enriched between groups. Notably, patients with HAM (the most advanced, symptomatic stage) exhibited decreased Faecalibacterium, a genus recognized for its anti-inflammatory, butyrate-producing commensal members, alongside increases in other bacteria.

What are the greatest implications of this study?

These findings suggest gut microbiome alterations, including loss of anti-inflammatory commensals like Faecalibacterium, may be linked to disease progression from asymptomatic HTLV-1 carriage to HAM/TSP. This supports extending the gut-brain axis framework, already established in diseases like multiple sclerosis, to HTLV-1-associated neuroinflammation. The results position the gut microbiome as a potential area for further investigation in understanding or monitoring HAM/TSP progression.

What was studied?

Epidemiological studies have highlighted an association between periodontitis and osteoporosis. However, the mechanism underlining this association remains unclear. Here, we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients, with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria. Using an ovariectomized (OVX) mouse model, we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota. Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism. The tryptophan metabolite indole-3-lactic acid (ILA) directly inhibited osteoclast formation and differentiation. In OVX mice treated with periodontitis salivary microbiota, supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones. In summary, our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.

What was studied?

This randomized, double-blind, placebo-controlled trial tested whether daily supplementation with two specific probiotic strains, Bifidobacterium animalis subsp. lactis XLTG11 and Lactiplantibacillus plantarum CCFM8661, could reduce recurrent respiratory tract infections (RRTIs) in children. Over 180 days, the study tracked infection frequency and duration alongside changes in gut microbiota composition, functional metabolic pathways, and immune biomarkers. The design allowed the researchers to link clinical respiratory outcomes to underlying shifts in the gut microbial community and immune regulation.

Who was studied?

The study enrolled 120 children who had been diagnosed with recurrent respiratory tract infections. Participants were randomly assigned to receive either the probiotic combination or a matched placebo daily for 180 days. The abstract does not provide further demographic details such as age range or sex distribution.

What were the most important findings?

Children receiving the probiotics had significantly reduced duration and frequency of fever, cough, upper respiratory tract infections, trachea or bronchitis, pneumonia, and overall RRTI recurrence compared with placebo (all p < 0.05). Gut microbiota profiling at day 180 showed clear community differences between groups, with the probiotic group showing greater abundance of beneficial commensal taxa and the placebo group showing more opportunistic genera. Functional pathway analysis pointed to enhanced metabolic stability in the probiotic recipients, and immune biomarker patterns showed comparatively stable IgG, IgM, and complement C3 levels, suggesting a more regulated humoral immune response. Growth trajectories remained normal in both groups.

What are the greatest implications of this study?

These findings support strain-defined probiotic supplementation as a viable adjunct strategy for reducing the burden of recurrent respiratory infections in children. The parallel shifts in gut microbial composition, metabolic function, and humoral immune stability suggest the respiratory benefit may be mediated through gut-immune axis modulation rather than a direct respiratory-tract effect. Because growth remained normal, the intervention appears well tolerated over a six-month period, supporting its potential for longer-term pediatric preventive use pending further confirmatory trials.

What was studied?

Silicosis is an irreversible and progressive form of pulmonary fibrosis resulting from inhalation of silica particles, representing a persistent global health concern. Although the gut microbiota has been implicated in chronic lung diseases, its role in silicosis remains largely unexplored. Here, we performed 16S ribosomal RNA (rRNA) gene sequencing on fecal samples from 78 silicosis patients (27 stage I, 24 stage II, 27 stage III) and 30 matched healthy controls (HCs), and further conducted untargeted fecal metabolomics profiling in stage I patients, the critical point for microbial dysbiosis. Silicosis patients exhibited significantly altered beta diversity compared with HCs. At the phylum level, a progressive increase in Proteobacteria and a decline in Bacteroidota were observed. Notably, Pantoea, Kluyvera, and unclassified Pasteurellaceae were significantly enriched in stage I patients, with persistent alterations across later stages, suggesting stage I as a key turning point of microbial dysbiosis. Metabolomic analysis of stage I patients revealed distinct profiles enriched in tyrosine, histidine, purine metabolism, and arginine biosynthesis pathways. Correlation analysis identified strong associations between specific taxa and metabolites, and combined microbial-metabolite signatures such as Lactobacillus with N-succinyl-2-amino-6-ketopimelate (N-Succinyl-AKP) achieved an area under the curve (AUC) of 0.84 in distinguishing stage I patients from HCs.IMPORTANCEThis study systematically characterizes gut microbial changes across different stages of silicosis and integrates microbiome-metabolome data specifically in early-stage patients. We demonstrate that stage I is a critical point for gut microbiome alterations and identify microbe-metabolite signatures with diagnostic potential. These findings highlight the gut microbiome-metabolome combination as a promising source of non-invasive biomarkers for the early detection of silicosis.

What was studied?

The contribution of human milk (HM) microbiota to infant gut health was addressed by evaluating the impact of HM bacteria, combined in two synthetic communities (SynComs) exhibiting anti-inflammatory (AI) or high immunomodulatory (HI) properties in vitro, on gut immune and barrier functions, and microbiota. Neonatal mini-piglets were fed either a formula without supplementation (CTRL) or supplemented with AI or HI SynComs and were compared to sow milk-fed (SM) piglets over a period of 24 days. Feces were collected on postnatal day (PND) 8, and ileal, colonic, and fecal samples were collected on PND24. The multifactorial analysis indicated that the two HM-derived SynComs impacted microbiota and intestinal functions differently. Several genera, mainly belonging to Bacillota, displayed different relative abundances between the formula-fed groups at both PND8 and PND24. At PND8, the fecal secretory IgA (sIgA) level in HI piglets was slightly lower than in SM piglets but markedly higher than in CTRL and AI piglets. SynComs HI and/or AI slightly increased the expression of genes involved in pro-inflammatory (IL6, TNFaR1), antioxidant (SOD2), anti-inflammatory (SOCS3), and Treg (FOXP3) pathways in ileal and colonic tissues compared with the CTRL group. Systemic immune functions were also modulated with a cytokine secretion capacity of peripheral blood mononuclear cells that tended to be higher with HI supplementation. Interestingly, SynCom bacteria were correlated with several ileal and colonic genera, and both were correlated with physiological variables. Overall, our findings support the influence of HM bacteria, provided in formulas as SynCom at a physiological concentration, on gut microbiota and functions.IMPORTANCEEarly-life environmental factors, such as neonatal diet, influence the gut microbiota, which plays a key role in the functional development of the gut. However, the role of the human milk (HM) microbiota, particularly with regard to the immunomodulatory properties of HM bacteria, is not well understood. This study investigates the differential effects of two synthetic communities with a similar taxonomic composition representative of the taxonomic diversity of the HM microbiota. These communities exhibit contrasting immunomodulatory properties that were previously characterized using an in vitro intestinal quadricellular model. Daily supplementation with these two SynComs modulated the composition of the gut microbiota and the gut physiology differently, particularly the intestinal immune signatures. In conclusion, the functional profile of bacteria within the HM microbiota may induce distinct developmental profiles of gut physiology in infants.

What was studied?

Our prior research revealed that dietary nitrate (NO₃⁻) may mitigate alcohol-induced cognitive impairment through oral microbiota modulation and attenuation of inflammatory responses in mice. While alcohol use disorder (AUD) is known to associate with cognitive decline and gut dysbiosis, the therapeutic potential of nitrate supplementation in ameliorating these effects remains to be elucidated. In this randomized, double-blind, placebo-controlled pilot trial (NCT05963659), 70 AUD patients received either nitrate-rich beetroot juice or placebo for 14 days. Primary outcomes were spatial memory measured by Cambridge Neuropsychological Test Battery. Oral and gut microbiota were analyzed before and after intervention by 16S rRNA sequencing. To establish causality, germ-free (GF) mice were colonized with pre- and post-nitrate intervention saliva samples from AUD patients, followed by microbiota profiling across gastrointestinal regions. The mean difference in Delayed Matching to Sample (all delays) change between the nitrate consumption group and the placebo group after intervention was 9.784 (95%[CI], 1.85-17.72, P = 0.016), as analyzed using a generalized linear mixed model. Nitrate supplementation induced distinct shifts in oral microbiota, while gut microbiota exhibited less pronounced changes. GF mice receiving pre-intervention microbiota exhibited elevated Klebsiella abundance throughout the gut. Mechanistically, nitrate attenuated systemic inflammation, enhanced intestinal barrier integrity, and improved cognitive performance in mice. Dietary nitrate enhances cognitive function in AUD patients, partially mediated by ectopic colonization of oral microbiota. Our findings identify specific oral bacteria (e.g., Klebsiella) as key contributors to alcohol-induced cognitive impairment and suggest promising therapeutic potential for microbiota-targeted interventions in AUD.

What was studied?

High-fat diet (HFD) consumption contributes to obesity, yet its impact on females of (pre)reproductive age and the effects of dietary modification after adolescence remain underexplored. This study examined how continuous HFD exposure or an adolescent switch from HFD to a standard diet (SD) shapes the gut microbiome, behavior, neurochemistry, metabolism, and key components of the hypothalamic-pituitary-adrenal (HPA) axis in female rats. Because HPA-axis alterations can occur across generations after HFD exposure, we examined reproductive-tissue HPA-axis components as potential mechanisms of transmission. Females received SD, HFD, or HFD followed by SD after majority of adolescence (postnatal day 60). HFD exposure impaired HPA-axis regulation and switching to SD during adolescence did not prevent persistent dysfunction into adulthood. However, reproductive HPA-axis components remained unaltered. Diet also strongly influenced the microbiome: while HFD disrupted microbial composition in adolescence, switching to SD partially restored it by adulthood. Behavioral and metabolic effects, including increased adiposity and anxiety-like behavior, emerged only with prolonged HFD exposure. Brain neurotransmitter concentrations remained largely unaffected. Overall, dietary history across adolescence and early adulthood shaped long-term HPA-axis function, microbiome composition, and behavioral outcomes. The absence of reproductive HPA-axis alterations suggests it is not a major mediator of maternal HFD-induced intergenerational effects. Persistent HPA-axis dysfunction despite dietary switching indicates limited reversibility, whereas the microbiome showed the greatest adaptive capacity. In contrast, lasting behavioral and metabolic consequences of HFD require continued exposure to adulthood.

What was studied?

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain, altered bowel habits, and frequent comorbidity with anxiety and depression. The gut microbiota has been implicated in gut-brain axis (GBA) dysfunction, but consistent microbial signatures remain unclear. We performed whole metagenome shotgun sequencing of stool samples from 63 female patients with moderate to severe IBS and 34 female healthy controls and assessed microbial composition and functional pathways. Microbial richness and diversity were slightly reduced in IBS, though with high variability and no robust separation from controls. Differential abundance analyses revealed enrichment of Streptococcus sp. and the sulfate-reducing bacterium Desulfovibrio piger in IBS, alongside reductions in Bifidobacterium and Methanobrevibacter. Functional profiling identified 39 differentially abundant pathways: amino acid biosynthesis (e.g., L-isoleucine, L-threonine) was more prominent in IBS, while carbohydrate degradation pathways (e.g., galactose, stachyose) were enriched in healthy controls. These findings indicate modest but significant IBS-associated shifts in gut microbial composition and function that may contribute to IBS symptoms. However, high intra-group variability underscores the complexity of IBS and highlights the need for larger, multi-omics studies to define robust microbial markers. These results contribute to a growing body of evidence emphasizing the complexity of gut microbiota-host interactions and the need for high-resolution, systems-level approaches in microbiome-associated disorders.

What was studied?

In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment.

Who was studied?

We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment.

What were the most important findings?

Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight.

What are the greatest implications of this study?

Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

What was studied?

Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease.

Who was studied?

Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence.

What were the most important findings?

A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features.

What are the greatest implications of this study?

Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

What was studied?

Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid.

What were the most important findings?

Bacterial invasion of colonic crypts was observed in CVID (3/15) and X-linked agammaglobulinemia (XLA, 1/3), but not in healthy control (HC, 0/9) biopsies. Fecal gut microbiota was characterized using 16S rRNA-targeted amplicon sequencing. Increased bacterial load, decreased alpha diversity and distinct beta diversity were observed in CVIDid (n = 42) compared to HC (n = 48), and similar results were seen in CVID with IgA deficiency (n = 40) compared to HC. CVIDid and CVID-IgA showed enrichment of the genus Enterococcus, and in vitro studies confirmed the inflammatory potential of Enterococcus gallinarum and Enterococcus hirae in patient monocytes.

What are the greatest implications of this study?

This study further supports the hypothesis that a dysregulated gut microbiota, with IgA deficiency as an important driving factor, contributes to systemic inflammation in primary antibody deficiency, and introduces enterococci as potential pathobionts in CVIDid. Video Abstract.