Newborns with gastroschisis hospitalised in the neonatal intensive care unit (NICU) are at risk for a disrupted gut microbiome. Infants with gastroschisis are particularly vulnerable to a dysbiotic microbiome; they require prolonged parenteral nutrition (PN) due to intestinal dysmotility, which often leads to growth faltering (GF). This pilot study's goals were to (1) compare the gut microbiome in infants with gastroschisis to infants admitted to the NICU without congenital anomalies, (2) identify differences in the gut microbiome between infants with gastroschisis requiring prolonged PN and those who do not, and (3) compare the microbiome in infants with gastroschisis with GF to those without GF. This was a multi-site prospective cohort study including 17 infants born with gastroschisis and 16 infants with a gestational age greater than 34 weeks admitted to the NICU without congenital anomalies (controls). Prolonged PN was defined as more than 28 days. GF was defined as a decline in weight or length z-score from birth to discharge of ≤-0.8. Stool samples were collected weekly during hospitalisation and analysed by shotgun metagenomics to assess bacterial composition, diversity, and function. Gestational age and birth weight were similar in the gastroschisis group and the control group. Infants with gastroschisis showed increased Staphylococcus aureus and decreased Bifidobacterium longum. Those requiring prolonged PN had a reduced abundance of genes in the glucosidase pathway compared to those who did not. Infants with GF showed a lower abundance of genes involved in the NAD-diphosphatase pathway compared to those without GF. Infants with gastroschisis display a distinct microbial composition and function compared to NICU infants without this condition. Among infants with gastroschisis, differences in bacterial functional capacity were observed in those who required prolonged PN and developed GF.

Composition of the gut microbiota, and related short chain fatty acids (SCFAs) production can influence allergic status. Extensively hydrolysed casein (eHC) infant formulas are used for management of cow's milk protein (CMP) allergy; however, effects of eHC on gut microbiota as a potential mechanism contributing to benefits of eHC for infants with allergy are not well understood. This exploratory study aimed to assess the in vitro effects of eHC on infant gut microbial composition and metabolism. Two batches of a specific eHC preparation, along with a mixture of individual amino acids (AA), were first digested in the in vitro TNO Intestinal Model-1 (TIM-1) simulating infant upper gastrointestinal digestion conditions followed by an in vitro colon fermentation model inoculated with faeces from healthy, formula-fed infants. Peptide profile after digestion of the test compounds, as well as effects of the compounds on microbiota community structure and SCFA production were assessed. Overall peptide profiles of the eHC preparations (qualitative, based on liquid chromatography-mass spectrometry) remained largely unaffected by simulated upper gastrointestinal digestion. Faecal fermentation of the specific eHC preparations influenced microbiota composition, with a major impact on Bacteroides abundance. SCFA production was increased beyond control conditions by eHC but not AA. The impact of the AA mixture differed considerably from that of the eHC containing specific peptides. Results suggest that eHC formulas can impact microbiota composition and SCFA production in an in vitro colon fermentation model. While the descriptive results of this study require future confirmation under a more extensive experimental setup, it can be hypothesised that mechanisms modulating microbiota composition and metabolism occurring in infants fed with eHC formula for the management of CMP allergy might contribute to clinical observations related to allergy and tolerance development.

The implication of gut microbiota in the pathophysiology of type 2 diabetes, one of the major health concerns worldwide, has demonstrated the benefits of using probiotics to improve dysbiosis. Facing the lack of defined research strategy to found and qualify bacterial with real antidiabetic activity, we have developed a program to identify, select and validate novel strains able to improve metabolic alterations in type 2 diabetes. Among potential candidates, we identified Bacteroides faecichinchillae (named BAfa hereafter), and the present work presents the validation of the antidiabetic potential of the ST37 (DSMZ 26883) BAfa strain in mice fed a high-fat high-sucrose (HFS) diet for 10 weeks followed by 4 weeks of treatment. Daily gavage with live, but not heat inactivated, BAfa improved glucose tolerance, fasting hyperinsulinemia and liver triglyceride content in HFS fed mice. Furthermore, these beneficial effects were retained after lyophilization. Using this preclinical model, we characterised BAfa mechanism of action, showing that four weeks of treatment was associated with reduced hepatic accumulation of ceramides, key actors of insulin resistance. The underlying mechanism could be related to BAfa-induced changes in the intestinal bile acid profile and inhibition of the Fxr-Fgf15 pathway in the ileum. BAfa supplementation during 4 weeks in HFS fed mice was also associated with mild modifications of gut microbiota composition, with the upregulation of several species known for their beneficial metabolic actions (such as Lactobacillus johnsonii, Limosilactobacillus reutei, Roseburia, Turicimonas muris, Phocaeicola dorei or Akkermansia muciniphila) and for being up-regulated during metformin treatment. Altogether, these data indicate that BAfa and related B. faecichinchillae strains could be considered for developing next-generation probiotics to treat type 2 diabetes, potentially in combination with the anti-diabetic drug metformin.

Topical probiotic formulations containing live bacteria are being explored as treatments for skin disorders such as atopic dermatitis and acne vulgaris. Certain bacterial strains with antimicrobial and/or anti-inflammatory properties show promise as bacterial therapeutics that could improve these conditions and serve as alternatives to antibiotics, which are increasingly compromised by rising antimicrobial resistance. However, little is known about the engraftment efficacy of such bacterial strains or their impact on the native skin microbiome. In this study, we applied two different coagulase-negative staphylococcal strains, one with antimicrobial activity (Staphylococcus epidermidis 2C-5) and one lacking any activity (Staphylococcus hominis H2-S92), on human back skin of 14 healthy volunteers. Engraftment was assessed using strain-specific PCR and three amplicon-based sequencing approaches at 7 and 30 days after application. Microbial profiles shifted modestly, showing a relative increase in staphylococci and a decrease in Cutibacterium spp. S. epidermidis 2C-5 drastically increased from 0.8% pre-application to 46.9% and 12.1% at days 7 and 30, respectively. S. hominis H2-S92 showed a relative rise from 1.4% to 35.8% at day 7, declining to 2.4% by day 30. Interestingly, Staphylococcus capitis relative abundance decreased by 50-60% at the application sites. These findings indicate that both strains can temporarily engraft and competitively displace native staphylococci. S. epidermidis 2C-5 appeared to colonize more effectively, possibly due to its bacteriocin production. Neither strain affected the phylotype composition of Cutibacterium acnes, suggesting lack of reach to sebaceous follicles, C. acnes' primary niche. This study supports the potential of staphylococcal probiotics for modulating the skin microbiome. While they may be effective for conditions involving staphylococcal dysbiosis, such as atopic dermatitis, they appear less suited for treating disorders like acne vulgaris, which are associated with C. acnes imbalance.

A large fraction of the intestinal microbiota is highly coated with secretory IgA, and bacteria-specific IgA is believed to shape the composition of the microbiota. A hallmark of the adaptive immune system is immunological memory to specific antigens. However, whether there is strong and persistent memory of secretory antibodies to bacterial antigens has not been determined. Here we show that ultra long-lived CD19-CD45- (age > 20 years) plasma cells (PCs) residing in the human small intestine produce IgA that binds to most taxa of a diverse anaerobic microbiota culture. Long-lived CD19-CD45+ (age > 10 years) and short-lived CD19+CD45+ (age < 2 years) PCs also produced IgA with broad bacterial reactivity. A clear correlation between high-binding and low-binding taxa was observed across the PC subsets. We also found that host PCs were depleted in acute intestinal graft versus host disease, a condition strongly associated with loss of microbiota diversity. Together, we show that bacterial antigens in the intestine induce an extremely stable, long-lasting humoral immune memory that may be important for the long-term stability and resilience of the intestinal microbiome.

This double-blinded randomised controlled trial investigated whether menaquinones (MK) producing probiotics for 12 weeks improve vitamin K status, compared with placebo in 50-75 years old with at least one cardiovascular risk factor. Twenty participants were randomised to either MK-producing probiotics (n= 10) or placebo (n= 10). Plasma dephosphorylated-uncarboxylated matrix gla protein (dp-ucMGP) concentrations were the primary study outcome and determined at baseline, six and twelve weeks by a chemiluminescent InaKtif MGP assay, and analysed by linear mixed models. Secondary outcomes included serum MK-7 and phylloquinone and stool MK-4 to MK-10 and phylloquinone, assessed by linear regression. Three participants dropped out (two placebo, one intervention). Compliance was high; median 98% [IQR 96-99] and 90% [IQR 74-96] sachets used in intervention vs placebo arm. At 6 weeks, dp-ucMGP was significantly lower in the intervention group (-75.69 [95%-CI -128.37; -22.92] pmol/l), but this difference diminished by 12 weeks (-38.63 [95%-CI -94.49; 16.14] pmol/l) due to a reduction in the placebo group. Overall, the mean dp-ucMGP change over 12 weeks favoured the intervention (-59.89 [95%-CI -110.7; -9.187] pmol/l). Statistically significant differences in secondary outcomes included higher serum MK-7, and faecal MK-6 and MK-7 concentrations in the probiotic vs placebo arm (e.g. 4.41 [95%-CI 2.17; 6.65]μg/L for serum MK-7). No other secondary outcomes differed significantly. MK producing probiotics may enhance vitamin K status in older adults at elevated cardiovascular risk. Larger, longer-term studies are needed to assess functional outcomes. The Netherlands Trial Register: NTR7505, 27-09-2018.

Fermented milk containing Lacticaseibacillus paracasei strain Shirota (LcS) has been shown to improve stool consistency in various countries; however, its effect on hard or lumpy stools (HLS) in the Vietnamese population remains unclear. We investigated the effects of LcS-fermented milk on constipated Vietnamese adults with a high prevalence of HLS. In a single-centre, open-label trial, 51 participants with HLS were randomised to receive one bottle per day of fermented milk containing ≥6.5× 109 cfu of LcS for 4 weeks (probiotic group) or no intervention (control group), followed by a 2-week washout. The primary endpoint was the proportion of participants with HLS (Bristol Stool Form Scale score of 1 or 2) in ≥25% of bowel movements over 4 weeks. Secondary endpoints included total stool frequency, HLS frequency, ideal stool form, and defecation-related symptoms - all recorded in daily diaries. The Chinese Constipation Questionnaire (CCQ) and gut microbiota composition (16S rRNA sequencing) were assessed every 2 weeks. During the intervention, the probiotic group had a significantly lower proportion of participants with HLS in ≥25% of bowel movements compared to controls (odds ratio: 0.00; 95% confidence interval: 0.00-0.16; P = 0.005). The probiotic group also showed increased total stool frequency ( P = 0.001), reduced HLS frequency ( P = 0.035), and fewer participants with CCQ scores ≥5 indicating constipation ( P < 0.001) at 4 weeks. Gut microbiota beta-diversity differed between groups after 2 weeks ( P = 0.031), with reductions in Peptococcaceae, Clostridium_methylpentosum_group, and Clostridia (unclassified at the order level), followed by increases in Lachnospiraceae_UCG-004 at 4 weeks and Lachnospiraceae_ND3007_group post-follow-up ( P < 0.050), suggesting microbial changes linked to constipation improvement. No serious adverse events related to the intervention were observed. These findings support daily LcS-fermented milk as a dietary strategy in Vietnam to manage constipation via gut microbiota modulation. The study was registered at ClinicalTrials.gov (ID: NCT05982743).

Oxidative stress is a significant contributor to neuronal damage in multiple sclerosis (MS), marked by an imbalance in reactive oxygen species and antioxidant defences. Probiotics may modulate oxidative stress and improve antioxidant levels. This double-blind, randomised, placebo-controlled clinical trial aimed to evaluate the effects of probiotics supplementation on serum oxidative stress markers and endogenous antioxidants in patients with relapsing-remitting MS (RRMS). Ninety RRMS patients with expanded disability status scale [EDSS]< 4 were randomised into two groups: a probiotics group (Lactocare®) and a placebo group, and received the interventions twice daily for four months. Serum levels of oxidative stress markers (malondialdehyde [MDA]), endogenous antioxidants (glutathione peroxidase [GPx] activity, superoxide dismutase [SOD], catalase activity [CAT], glutathione [GSH]), and total antioxidant capacity (TAC) were measured at baseline and post-treatment. Fifty-five patients, including 26 patients in the probiotic group and 29 patients in the placebo group, completed the study. Both groups showed significant within-group improvements in GPx activity, SOD, and GSH levels, as well as reductions in MDA levels ( P < 0.05); however, no significant between-group differences were found for any markers ( P > 0.05). TAC and CAT levels remained unchanged in both groups. Findings of this study did not support the evidence for antioxidant effects of probiotics supplementation in RRMS patients, and its effects on oxidative stress markers in RRMS patients are found to be comparable to placebo. Iranian Registry of Clinical Trials: IRCT20220713055465N2, registration date: 2023.5.9.

Chronic alcoholism can result in alcoholic liver disease. Current treatment methods for alcoholic liver injury primarily include abstinence, drug therapy, and surgical treatment. However, these methods have their own shortcomings - abstinence does not cure alcoholic liver disease, drug therapy can produce negative side effects, and surgical treatment is often accompanied by risks, specifically liver rejection. Therefore, it is especially important to find a safe and effective method to ameliorate alcoholic liver disease. Probiotics, as natural microorganisms in the human intestine, can effectively alleviate alcoholic liver disease due to their unique properties. While Lactiplantibacillus (Lpb.) plantarum, a representative strain of probiotics, has been shown to exert beneficial effects against alcoholic liver injury, the underlying mechanism is unclear. In this study, a murine model of alcoholic liver injury was established in C57BL/6 mice by feeding mice a Lieber-DeCarli diet for 2 weeks. This model was then utilised to assess the potential protective mechanism of Lpb. plantarum LP4. The results demonstrated that Lpb. plantarum LP4 could significantly decrease pro-inflammatory cytokines in serum and liver, thereby reducing the inflammatory response. Furthermore, treatment with Lpb. plantarum LP4 inhibited inflammation and oxidative stress in the liver by modulating several signalling pathways. In addition, Lpb. plantarum LP4 also prevented endotoxin-induced hepatic injury by protecting the integrity of the intestinal barrier. In conclusion, Lpb. plantarum LP4 can effectively alleviate alcoholic liver injury in C57BL/6 mice.

Obesity is a growing public health concern in the Middle East and North Africa (MENA) region, yet limited research has explored how gut microbiota varies between Arab populations. This study compared the gut microbiota composition and diversity of Emirati and Lebanese adults with obesity and assessed the role of age and nationality in shaping microbial variation. A total of 43 Emirati and 30 Lebanese individuals with obesity (body mass index (BMI) ≥35kg/m2) were recruited. Participants provided anthropometric and biochemical data, dietary records, and stool samples for 16S rRNA sequencing. The analysis revealed significantly higher BMI, weight, and fat mass in Emirati participants, while Lebanese individuals reported higher fibre intake. Taxonomic profiling showed higher relative abundances of Pseudomonadota, Mycoplasmatota, Cyanobacteriota, and Lentisphaerota in the Lebanese group, whereas Bacteroidota was more abundant among Emiratis. Lebanese participants also exhibited significantly greater microbial alpha-diversity. Beta-diversity analysis confirmed clear distinctions in microbial community structure between the two groups. Linear Discriminant Analysis Effect Size (LefSe) (LDA score >10log2) and regression models ( P < 0.05) identified specific bacterial genera associated with nationality, although these associations were attenuated after adjusting for age. These findings suggest that gut microbiota in Arab populations is influenced by demographic, dietary, and environmental factors, emphasising the need for culturally tailored microbiota-based strategies to manage obesity and related metabolic conditions.