The human microbiome is increasingly recognized for its crucial role in the development and progression of neurodegenerative diseases. While the gut-brain axis has been extensively studied, the contribution of the oral microbiome and gut-oral tropism in neurodegeneration has been largely overlooked. Cognitive impairment (CI) is common in neurodegenerative diseases and develops on a spectrum. In Parkinson's Disease (PD) patients, CI is one of the most common non-motor symptoms but its mechanistic development across the spectrum remains unclear, complicating early diagnosis of at-risk individuals. Here, we generated 228 shotgun metagenomics samples of the gut and oral microbiomes across PD patients with mild cognitive impairment (PD-MCI) or dementia (PDD), and a healthy cohort, to study the role of gut and oral microbiomes on CI in PD. In addition to revealing compositional and functional signatures, the role of pathobionts, and dysregulated metabolic pathways of the oral and gut microbiome in PD-MCI and PDD, we also revealed the importance of oral-gut translocation in increasing abundance of virulence factors in PD and CI. The oral-gut virulence was further integrated with saliva metaproteomics and demonstrated their potential role in dysfunction of host immunity and brain endothelial cells. Our findings highlight the significance of the oral-gut-brain axis and underscore its potential for discovering novel biomarkers for PD and CI.

Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding Porphyromonadaceae, Campylobacteraceae, Prevotellaceae, Actimomycetaceae, Veillonellaceae, Anaerivoracaceae, Fusobacteriaceae, and the Clostridium family XI 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while Pseudomonadaceae and Micrococcacecae, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.

The human gut microbiota has gained interest as an environmental factor that contributes to health or disease. The development of next-generation live biotherapeutic products (LBPs) is a promising strategy to modulate the gut microbiota and improve human health. In this study, we identified a novel cross-feeding interaction between Bacteroides xylanisolvens and Clostridium butyricum and developed their combination into a novel LBP for treating metabolic syndrome. Using in-silico analysis and in vitro experiments, we demonstrated that B. xylanisolvens supported the growth and butyrate production of C. butyricum by supplying folate, while C. butyricum reciprocated by providing pABA for folate biosynthesis. Animal gavage experiments showed that the two-strain combination LBP exhibited superior therapeutic efficacy against metabolic disorders in high-fat diet-induced obese (DIO) mice compared to either single-strain treatment. Further omics-based analyses revealed that the single-strain treatments exhibited distinct taxonomic preferences in modulating the gut microbiota, whereas the combination LBP achieved more balanced modulation to preserve taxonomic diversity to a greater extent, thereby enhancing the stability and resilience of the gut microbiome. Moreover, the two-strain combinations more effectively restored gut microbial functions by reducing disease-associated pathways and opportunistic pathogen abundance. This work demonstrates the development of new LBP therapy for metabolic diseases from cross-feeding microbial pairs which exerted better self-stability and robust efficacy in complex intestinal environments compared to conventional single-strain LBPs.

Metagenomic sequencing deepened our knowledge about the role of the intestinal microbiota in human health, and several studies with various methodologies explored its dynamics during antibiotic treatments. We compared the impact of four widely used antibiotics on the gut bacterial diversity. We used plasma and fecal samples collected during and after treatment from healthy volunteers assigned to a 5-day treatment either by ceftriaxone (1 g every 24 h through IV route), ceftazidime/avibactam (2 g/500 mg every 8 h through IV route), piperacillin/tazobactam (1 g/500 mg every 8 h through IV route) or moxifloxacin (400 mg every 24 h through oral route). Antibiotic concentrations were measured in plasma and feces, and bacterial diversity was assessed by the Shannon index from 16S rRNA gene profiling. The relationship between the evolutions of antibiotic fecal exposure and bacterial diversity was modeled using non-linear mixed effects models. We compared the impact of antibiotics on gut microbiota diversity by simulation, using various reconstructed pharmacodynamic indices. Piperacillin/tazobactam was characterized by the highest impact in terms of intensity of perturbation (maximal [IQR] loss of diversity of 27.3% [1.9; 40.0]), while moxifloxacin had the longest duration of perturbation, with a time to return to 95% of baseline value after the last administration of 13.2 d [8.3; 19.1]. Overall, moxifloxacin exhibited the highest global impact, followed by piperacillin/tazobactam, ceftazidime/avibactam and ceftriaxone. Their AUC between day 0 and day 42 of the change of diversity indices from day 0 were, respectively, -13.2 Shannon unit.day [-20.4; -7.9], -10.9 Shannon unit.day [-20.4; -0.6] and -10.1 Shannon unit.day [-18.3; -4.6]. We conclude that antibiotics alter the intestinal diversity to varying degrees, both within and between antibiotics families. Such studies are needed to help antibiotic stewardship in using the antibiotics with the lowest impact on the intestinal microbiota.

The role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influence weight gain in humans, to induce weight gain in C57BL/6J female mice. We hypothesized that microbes essential for maintaining gut homeostasis and energy balance would be depleted following treatment with risperidone, leading to enhanced weight gain relative to controls. Thus, we performed metagenomic analyses on stool samples to identify microbes that were excluded in risperidone-treated animals but remained present in controls. We identified multiple taxa including Limosilactobacillus reuteri as a candidate for further study. Oral supplementation with L. reuteri protected against risperidone-induced weight gain (RIWG) and was dependent on cellular production of a specialized metabolite, reutericyclin. Further, synthetic reutericyclin was sufficient to mitigate RIWG. Both synthetic reutericyclin and L. reuteri restored energy balance in the presence of risperidone to mitigate excess weight gain and induce shifts in the microbiome associated with leanness. In total, our results identify reutericyclin production by L. reuteri as a potential probiotic to restore energy balance induced by risperidone and to promote leanness.

Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.

Next-generation live biotherapeutics are promising to aid the treatment of obesity and metabolic diseases. Here, we reported a novel anti-obesity probiotic candidate, Roseburia hominis, that was depleted in stool samples of obese subjects compared with lean controls, and its abundance was negatively correlated with body mass index and serum triglycerides. Supplementation of R. hominis prevented body weight gain and disorders of glucose and lipid metabolism, prevented fatty liver, inhibited white adipose tissue expansion and brown adipose tissue whitening in mice fed with high-fat diet, and boosted the abundance of lean-related species. The effects of R. hominis could be partially attributed to the production of nicotinamide riboside and upregulation of the Sirtuin1/mTOR signaling pathway. These results indicated that R. hominis is a promising candidate for the development of next-generation live biotherapeutics for the prevention of obesity and metabolic diseases.

The development of cardiometabolic (CM) diseases is associated with chronic low-grade inflammation, partly linked to alterations of the gut microbiota (GM) and reduced intestinal integrity. The SINFONI project investigates a multifunctional (MF) nutritional strategy's impact combining different bioactive compounds on inflammation, GM modulation and CM profile. In this randomized crossover-controlled study, 30 subjects at CM-risk consumed MF cereal-products, enriched with polyphenols, fibers, slowly-digestible starch, omega-3 fatty acids or Control cereal-products (without bioactive compounds) for 2 months. Metabolic endotoxemia (lipopolysaccharide (LPS), lipopolysaccharide-binding protein over soluble cluster of differentiation-14 (LBP/sCD14), systemic inflammation and cardiovascular risk markers, intestinal inflammation, CM profile and response to a one-week fructose supplementation, were assessed at fasting and post mixed-meal. GM composition and metabolomic analysis were conducted. Mixed linear models were employed, integrating time (pre/post), treatment (MF/control), and sequence/period. Compared to control, MF intervention reduced intestinal inflammation (fecal calprotectin, p = 0.007) and endotoxemia (fasting LPS, p < 0.05), without alteration of systemic inflammation. MF decreased serum branched-chain amino acids compared to control (p < 0.05) and increased B.ovatus, B.uniformis, A.butyriciproducens and unclassified Christensenellaceae.CAG-74 (p < 0.05). CM markers were unchanged. A 2-month dietary intervention combining multiple bioactive compounds improved intestinal inflammation and induced GM modulation. Such strategy appears as an effective strategy to target low-grade inflammation through multi-target approach.

The evidence suggests that the microbiome plays a crucial role in cancer development. The oral cavity has many microorganisms that can influence oral cancer progression. Understanding the mechanisms and signaling pathways of the oral, gum, and teeth microbiome in tumor progression can lead to new treatment strategies. Probiotics, which are friendly microorganisms, have shown potential as anti-cancer agents. These positive characteristics of probiotic strains make them suitable for cancer prevention or treatment. The oral-gut microbiome axis supports health and homeostasis, and imbalances in the oral microbiome can disrupt immune signaling pathways, epithelial barriers, cell cycles, apoptosis, genomic stability, angiogenesis, and metabolic processes. Changes in the oral microbiome in oral cancer may suggest using probiotics-based treatments for their direct or indirect positive roles in cancer development, progression, and metastasis, specifically oral squamous cell carcinoma (OSCC). Here, reported relationships between probiotics, oral microbiota, and oral cancer are summarized.

Type 2 diabetes mellitus (T2DM) is a pervasive chronic metabolic disorder characterized by dysregulation of carbohydrate, protein, and lipid metabolism. The objective of this study was to elucidate the impact of multi-strain probiotic supplementation on the metabolism of carbohydrates and lipids and the interplay between the gut and liver in a T2DM rat model. A total of 32 rats were randomly assigned to four experimental groups: a control group, a T2DM model group, a low-dose probiotics group, and a high-dose probiotics group. The impact of probiotic intervention on glycemic and lipid profiles was evaluated, with a specific emphasis on the high-dose cohort. The treatment with multi-strain probiotics, consisting of three Lacticaseibacillus species and one Bifidobacterium species, resulted in a significant improvement in blood glucose and lipid profiles in T2DM rats, with the highest dosage demonstrating the most pronounced effects. Probiotic administration modulated gut microbiota composition and diversity, enriching potentially beneficial bacterial species and altering gut metabolic modules and carbohydrate-active enzyme profiles. Multi-omics analyses indicated that alterations in fecal short-chain fatty acids and serum bile acids may serve as pivotal mediators for crosstalk between hepatic and gut transcriptomic pathways. This study offers novel insights into the role of probiotics in managing T2DM via the gut-liver axis, emphasizing the potential of probiotic therapy in modulating key metabolic pathways.IMPORTANCEType 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia, caused by defects in insulin secretion, insulin action, or both. For individuals diagnosed with T2DM, managing diabetes-related complications is often the most challenging aspect. Exogenous probiotics have the potential to serve as a promising therapeutic strategy to improve diabetes-related symptoms. We conducted a 64-day animal experiment to investigate the effects of probiotics on T2DM-related metabolic disorders and dyslipidemia by feeding four mixed probiotics to T2DM rats. The results showed that probiotics exerted beneficial effects on glucose- and lipid-related homeostasis indices in diabetic rats to some extent and modulated the gut microbiota to manage T2DM via the gut-liver axis.

Dolutegravir (DTG) is increasingly replacing efavirenz (EFV) as the recommended first-line antiretroviral therapy (cART) component due to its superior tolerance. However, both EFV-based and DTG-based cART regimens are associated with metabolic and neuropsychiatric disorders through mechanisms that remain poorly understood. In this study, the abundance of Lactobacillus was significantly reduced, along with elevated soluble CD14 levels, in HIV-1-infected individuals receiving EFV-based cART compared to those on DTG-based cART. Additionally, EFV treatment in mice resulted in the destruction of intestinal crypts, loss of goblet cells, decreased expression of intestinal ZO-1, and more severe damage to gut barrier integrity compared to the DTG and normal control groups. Furthermore, we identified a significant reduction in Lactobacillus in EFV-treated mice. Our results suggest that EFV and DTG may directly lead to gut dysbiosis and compromised gut barrier integrity, which could be targeted to prevent the side effects associated with EFV and DTG.

Obesity is reaching global epidemic proportions worldwide, posing a significant burden on individual health and society. Altered gut microbiota is considered a key factor in the pathogenesis of many diseases, producing metabolites that contribute to the health-beneficial properties of postbiotics. Postbiotics, bioactive microbial components derived from probiotics, are emerging as a valuable strategy in modern medicine and a promising alternative for managing obesity without the need for live bacteria. This work provides a comprehensive overview of the potential health benefits of postbiotics, particularly in relation to obesity, which represents an important health challenge. Despite the encouraging insights into the health benefits of postbiotics, we highlight the need for further research to clarify the mechanisms and the specific roles of different postbiotic components. Integrating postbiotics into health interventions has the potential to enhance preventive care and significantly improve health outcomes in at-risk populations.

Recent advances in the study of the gut microbiota has pointed to its under-utilized source of potentially beneficial bacteria, known as next generation probiotics, offering a promising avenue to restore or compensate impaired gut microbiota toward a healthy state. Aside from the difficulties to achieve in-lab adequate culture conditions, the use of beneficial bacterial isolates is also limited by their bioavailability in the donor itself. In the iTARGET study, we positively selected donors based on their diet enriched in fiber, that has been shown to increase the prevalence of bacterial species associated with health. The iTARGET study is a monocenter, prospective, observational study of adults with healthy lifestyle and high daily fiber consumption. We aim to recruit individuals in two phases, the first one for all individuals that will permit the identification of carriers for bacteria of interest and the second phase for a subset of individuals to allow for culture and isolation of previously identified potentially beneficial bacteria. Our primary outcome is the isolation and culture of at least one potentially beneficial isolate. The secondary outcomes comprised the high throughput metagenomic profiles of the intestinal microbiota and the characterization of the cultured isolates. The study was approved by the French Research Ethics Committees (Comité de Protection des Personnes Sud-Est I) under the National reference ID 2023-A01677-38. Study findings and results will be published in peer-reviewed Open Access journals. (Trial registration number on ClinicalTrials.gov: NCT06166810).

The gut microbiome has emerged as a potential influencer of muscle health; however, its role in hospitalized patients remains unclear. This study aimed to investigate the association between gut microbiome diversity and skeletal muscle mass, strength, and quality in hospitalized post-stroke patients.

We conducted a cross-sectional study of post-stroke patients admitted to a rehabilitation facility. Gut microbiome diversity was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing, calculating Operational Taxonomic Unit (OTU) Richness, Faith's Phylogenetic Diversity (PD), and Shannon index. Muscle health was evaluated using skeletal muscle index (SMI) for muscle mass, handgrip strength (HGS) for muscle strength, and bioimpedance analysis-derived phase angle (PhA) for muscle quality. Multiple linear regression analyses were performed, adjusting for potential confounders.

A total of 156 patients (mean age 78.4 years; 55.7 % male) were analyzed. OTU Richness showed significant positive associations with SMI (β = 0.197, p = 0.025), HGS (β = 0.180, p = 0.005), and PhA (β = 0.178, p = 0.022). The Shannon index was also positively associated with SMI (β = 0.120, p = 0.041), HGS (β = 0.140, p = 0.028), and PhA (β = 0.164, p = 0.032). Faith's PD did not demonstrate significant associations with muscle health parameters.

Higher gut microbiome diversity, assessed by OTU Richness and Shannon index, is associated with better muscle mass, strength, and quality in post-stroke patients. These findings suggest a potential role for gut microbiota in muscle health during stroke rehabilitation.

Emerging science supports the role of lipid metabolism disorders in the occurrence and development of chronic diseases. Dietary intervention has been shown to be an effective strategy for regulating lipid metabolism. Recent studies showed that perilla is rich in various effective ingredients, including fatty acids, flavonoids, and phenolic acids. These ingredients exhibit a myriad of benefits, notably enhancing intestinal health and helping to manage metabolic diseases. Perilla oil stands out as a promising agent for regulating lipid metabolism, underscoring its potential for various health applications. This review introduces the active ingredients in perilla and provides a systematic overview of the mechanism by which perilla oil regulates lipid metabolism to expand its application value. Further research should focus on exploring the dose effect and absorption efficiency of perilla oil in clinical applications.

Emerging evidence suggests that bacteria residing in colorectal tissue are plausibly associated with colorectal cancer. Prior studies investigated the effects of dietary interventions on the fecal microbiome, but few assessed colorectal tissue microbiome endpoints. We investigated the effects of a high-fiber, high-fruit, high-vegetable, and low-fat dietary intervention on the rectal tissue microbiome in the Polyp Prevention Trial (PPT).

PPT is a 4-year randomized clinical trial with intervention goals of consuming (1) at least 18 g of fiber per 1000 kcal/day; (2) at least 3.5 servings of fruits and vegetables per 1000 kcal/day; and (3) no more than 20% of kcal/day from fat. Using 16S ribosomal RNA gene sequencing, we characterized bacteria in rectal biopsies collected at baseline and the end of years 1 and 4 (n = 233 in intervention arm and n = 222 in control arm). We estimated effects of the intervention on alpha and beta diversity and relative abundance of a priori-selected bacteria using repeated-measures linear mixed-effects models.

The intervention did not statistically significantly modify rectal tissue alpha diversity. Compared with the control arm, relative abundance of a priori-selected Porphyromonas (absolute intervention effects [standard errors] at T1 vs T0 = -0.24 [0.07] and T4 vs T0 = -0.12 [0.07]; P = .004) and Prevotella (absolute intervention effects at T1 vs T0 = -0.40 [0.14] and at T4 vs T0 = -0.32 [0.15]; P = .01) were more strongly decreased in the intervention arm.

The PPT intervention did not influence rectal tissue microbiome diversity or the relative abundance of most bacteria, except for 2 oral-originating bacteria that were previously associated with colorectal cancer presence.

Obesity is a risk factor for non-communicable diseases such as cardiovascular disease and diabetes, which are leading causes of death and disability. Today, China has the largest number of overweight and obese people, imposing a heavy burden on China's healthcare system. Obesity adversely affects the central nervous system (CNS), especially cognitive functions such as executive power, working memory, learning, and so on. The gradual increase in adult obesity rates has been accompanied by a increase in childhood obesity rates. In the past two decades, the obesity rate among children under 5 years of age has increased from 32 to 42 million. If childhood obesity is not intervened in the early years, it will continue into adulthood and remain there for life. Among the potential causative factors, early lifestyle may influence the composition of the gut flora in childhood obesity, such as the rate and intake of high-energy foods, low levels of physical activity, may persist into adulthood, thus, early lifestyle interventions may improve the composition of the gut flora in obese children. Adipose Axis plays an important role in the development of obesity. Adipose tissue is characterized by increased expression of nucleoside diphosphate-linked molecule X-type motif 2 (NUDT2), amphiphilic protein AMPH genes, which encode proteins that all play important roles in the CNS. NUDT2 is associated with intellectual disability. Furthermore, amphiphysin (AMPH) is involved in glutamatergic signaling, ganglionic synapse development, and maturation, which is associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD). All of the above studies show that obesity is closely related to cognitive decline in patients. Animal experiments have confirmed that obesity causes changes in cognitive function. For example, high-fat diets rich in long- and medium-chain saturated fatty acids may adversely affect cognitive function in obese mice. This process may be attributed to the Short-Chain Fatty Acid (SCFA)-rich high-fat diet (HFD) activating enterocyte TLR signaling, especially TLR-2 and TLR-4, altering the downstream MyD88-4 signaling, thereby impacting the downstream MyD88-NF-κB signaling cascade and up-regulating the levels of pro-inflammatory factors and lipopolysaccharide (LPS). These changes result in the loss of integrity of the intestinal mucosa and cause an imbalance in the internal environment. Obesity may lead to the disruption of the intestinal flora and damage the intestinal barrier function, causing intestinal flora dysbiosis. In recent years, a growing number of studies have investigated the relationship between obesity and the intestinal flora. For example, high-fat and high-sugar diets have been found to lead to the thinning of the mucus layer of the colon, a decrease in the number of tight junction proteins, and an increase in intestinal permeability in mice. Such changes alter the composition of intestinal microorganisms, allow endotoxins into the blood circulation, and induce neuroinflammation and brain damage. Therefore, obesity affects cognitive function and is even hereditary. This paper reviews the obesity-induced cognitive dysfunction, the underlying mechanisms, the research progress of intestinal flora dysregulation in obese patients, the relationship between intestinal flora and cognitive function changes, and the research progress on intestinal flora dysregulation in obese patients. We want to regulate the internal environment of obese patients from the perspective of intestinal flora, improving the cognitive function of obese patients, and prevent obesity-induced changes in related neurological functions.

Background: Pediatric obesity represents a multifactorial condition in which gut microbiota dysbiosis, low-grade systemic inflammation, and metabolic dysfunction are intricately connected. Objectives: This systematic review sought to evaluate and integrate current findings regarding the interactions between gut microbial composition, dietary influences, inflammatory status, and metabolic outcomes in obese pediatric populations. Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted for studies published from January 2010 onward. Eligible studies comprised randomized controlled trials, and cohort, cross-sectional, and longitudinal designs involving individuals aged ≤18 years. Study quality was appraised using the NIH Study Quality Assessment Tool. Results: Sixteen studies fulfilled the inclusion criteria. Dysbiosis was consistently observed among obese children, characterized by alterations in microbial diversity and abundance associated with increased inflammation and adverse metabolic profiles. Dietary interventions, notably symbiotic supplementation and adherence to Mediterranean diet patterns, were associated with favorable modulation of gut microbiota and inflammatory parameters. The majority of studies demonstrated high methodological quality, although minor observational limitations were noted. Conclusions: Gut microbiota dysregulation plays a central role in the development of metabolic and inflammatory complications associated with pediatric obesity. Although dietary and microbiota-modifying strategies show therapeutic promise, their effectiveness must be substantiated through robust, long-term studies.

Investigating the gut microbiome during host development is essential for understanding its influence on host health and fitness. While host body condition is a crucial fitness-related trait and a strong predictor of viability in numerous animal species, its relationship with gut bacteria remains underexplored, particularly in non-model organisms. This study examines the gut microbiome of the altricial wild bird species, yellow-rumped flycatchers (Ficedula zanthopygia), by analyzing nestling feces through 16S rRNA sequencing at four developmental stages: Day 3, Day 6, Day 9 and Day 12 post-hatching. We explored the temporal dynamics of the gut microbiome and its correlation with body condition, a key indicator of fitness. Our results demonstrate signinficant shifts in microbial community composition and diversity throughout development. Notably, Day 3 nestlings displayed lower alpha diversity compared to later stages, while microbial diversity stabilized from Days 6 to 12. Both the age of the nestlings and the environmental conditions of the nest box significantly shaped the gut microbial community structure. A contemporaneous relationship was observed, where the scaled-mass index (SMI) at Day 6 positively correlating with microbial diversity at that time. Additionally, a time-lagged effect emerged, linking SMI at Day 9 to microbial diversity at Day 6. These findings highlight the vital role of the gut microbiome in the development of nestlings, particularly emphasizing Day 6 as a critical period due to its stable microbial diversity and association with SMI. This study underscores the influence of gut bacteria on host fitness in developing birds.

In bottom-up proteomics, selecting an appropriate protein amino acid sequence database is vital for reliable peptide identification. However, this approach excludes species with unsequenced genomes, limiting the comprehensiveness. This is a major challenge in current microbiota proteomics, a rapidly developing field, which involves simultaneously assigning proteins to species in a sample and analyzing them using databases of protein amino acid sequences with known genomes. We aimed to develop a method to extend the database species diversity by generating protein amino acid sequences of unknown species using phylogenetic relationships among known species. To evaluate this approach, we generated the Helicobacter pylori F16 strain sequence based on the phylogenetic relationships of 29 closely related strains (excluding F16). Consequently, the percentages of peptides that matched the peptides obtained from the reference F16 strain increased by 5 %, based on sequence generation. Proteomics data analyses were performed on the F16 strain using the generated sequence database to validate peptide identification. Peptide spectral match decreased when the database was expanded using sequence generation owing to a decrease in sensitivity primarily caused by an increase in decoy hits. The decrease in identification sensitivity caused by large-scale databases could be improved by introducing a novel score, Ion Cover Score, based on spectral matching. The sequence generation method used in the present study and the introduction of scores based on spectral matching could accelerate proteomics development.

Obesity has become a global health crisis driven by genetic, environmental, and lifestyle factors, often linked to gut microbiome imbalances. Probiotics, particularly Lactobacillus and Bifidobacterium strains, have shown promise in clinical trials by promoting weight loss, improving lipid profiles, and addressing gut dysbiosis associated with obesity. This review surveys the literature on the microbiome and obesity, emphasizing the clinical relevance of probiotics in treatment strategies. Our comprehensive PubMed search highlights the mechanisms through which probiotics influence metabolic health, including their effects on inflammation and appetite regulation. We also explore promising future research directions and the potential for integrating probiotics into clinical practice. While results are encouraging, the evidence is limited by strain variability, small sample sizes, short trial durations, and individual differences in microbiota composition. More extensive, long-term studies with standardized methods are crucial to confirm the effectiveness of probiotics as viable anti-obesity treatments.

Dysbiosis of the gut microbiota is strongly implicated in atherosclerosis (AS), thus prompting microbial modulation to be explored as a therapeutic strategy. However, limited evidence exists for probiotic interventions capable of alleviating AS. Here, we focused on Clostridium butyricum (C. butyricum; CB), a probiotic known for its production of short-chain fatty acids (SCFAs). We found that administration of C. butyricum to high-fat diet (HFD)-fed Apoe deficient (Apoe-/-) mice reduced plaque area by improving blood lipid profiles, decreasing macrophage infiltration in the aortic roots, and lowering the levels of circulating pro-inflammatory monocytes and macrophages. By non-targeted serum metabolomics analysis, C. butyricum treatment significantly reduced the levels of both linoleic acid and its downstream metabolites. Collectively, these findings establish C. butyricum-mediated amelioration of AS through modulation of linoleic acid metabolism.

Obesity, insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic syndrome have been largely correlated to a reduction in bacterial load and diversity, resulting in a condition known as intestinal dysbiosis. The recent emergence of novel antidiabetic medications has been demonstrated to exert a favourable influence on the composition of the intestinal microbiota. Incretin-based therapy exerts a multifaceted influence on the composition of the gut microbiota, leading to alterations in bacterial flora. Of particular significance is the capacity of numerous metabolites produced by the gut microbiota to modulate the activity and hormonal secretion of enteroendocrine cells. This review examines the effects of dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and GLP-1/gastric inhibitory polypeptide (GIP) receptor dual agonists on the composition of the gut microbiota in both mice and human subjects. The nature of this interaction is complex and bidirectional. The present study demonstrates the involvement of the incretinic axis in modulating the microbial composition, with the objective of providing novel preventative strategies and potential personalised therapeutic targets for obesity and T2DM.

Mirroring the global obesity epidemic, obesity rates in inflammatory bowel disease (IBD) patients is rising. Several epidemiological studies propose that 15%-40% of adult patients with IBD are obese, and an additional 25%-40% fall into the overweight category. This article examines the pathophysiologic relationship between obesity and IBD concerning the role of visceral adipose tissue, microbiota shifts, dietary patterns, and hunger hormone changes. Additionally, increasing evidence is demonstrating the negative impact that obesity is having on disease course and quality of life in patients with IBD. Obesity has been demonstrated to be associated with an attenuated response to immunomodulators and biological agents, as well as higher rates of peri-operative surgical complications. A better understanding of the relationship between obesity and IBD can be applied to clinical decision-making in personalizing treatment plans, promoting weight loss in patients with obesity, and identifying areas of future research.

The specific influence of whole gut transit time (WGTT) on microbiome dynamics and bile acid metabolism remains unclear, despite links between changes in WGTT and certain gastrointestinal disorders. Our investigation aimed to determine the impact of WGTT changes on the composition of the fecal microbiome and bile acid profile.

Healthy volunteers (n = 18) received loperamide, to decrease bowel movement frequency, and senna, a laxative, each over a 6-day period, in a randomized sequence, with a minimum 16-day interval between each treatment. Stool samples were analyzed for microbiome by shotgun sequencing and bile acid composition determined with high-performance liquid chromatography coupled to tandem mass spectrometry. Sera were examined for markers of bile acid synthesis.

Senna or loperamide decreased or increased WGTT, respectively. Treatment altered stool characteristics, bowel movement frequency, and stool weight. The senna-treated group had increased primary and secondary fecal bile acids; serum levels of fibroblast growth factor 19 were significantly reduced. Increasing WGTT with loperamide led to an increase in bile salt hydrolase genes, along with elevated bacterial species richness (p = 0.04). Thirty-six species exhibiting significant differences were identified, several of which have notable implications for gut health. WGTT displayed negative correlations with total primary (particularly chenodeoxycholic acid) and secondary bile acids (ursodeoxycholic acid and glycochenodeoxycholic acid). Treatment-induced changes in microbiome composition and bile acid metabolism reverted back to baseline within 16 days.

Whole gut transit time changes significantly affect fecal microbiome composition and function, as well as bile acid composition and synthesis in healthy subjects. This consideration is likely to have long-term implications.

Previous studies have suggested that pesticide exposure and gut microbiome alterations are associated with gestational diabetes mellitus (GDM) risk. Understanding the complex interactive effect of these factors on GDM is essential. In a cohort of 852 pregnant women, we assessed pesticide levels in serum and analyzed the gut microbiota using 16S rRNA and shotgun metagenomic sequencing. We explored the interactions between pesticides and gut microbiota, assessed their roles in GDM development, and proposed a predictive model based on identified biomarkers. We identified an environmental risk score (ERS), denoting the pesticide mixture level significantly associated with GDM, with the gut microbiota, particularly involving the Dorea branch, playing a crucial mediating role. In addition, we found an interactive effect of pesticide exposure and gut microbiota on GDM risk. Notably, low Prevotella enrichment combined with high ERS arisen from pesticide levels led to a 10.36-fold increased GDM risk. The identified pesticide and gut microbial biomarkers achieved high predictive accuracy for GDM (AUC: 0.833, 95% CI: 0.748-0.918). Collectively, maternal pesticide exposure may induce disrupted microbiome-dependent glycemic alteration, necessitating future assessment of clinical implications. Potential GDM markers can serve as targets for therapeutic intervention caused by pesticides, leading to prevention.

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

The association between the microbiota and obstructive sleep apnea (OSA) remains understudied. In this study, we conducted a comprehensive systematic review and meta-analysis of studies investigating the diversity and relative abundance of microbiota in the gut, respiratory tracts and oral cavity of patients with OSA, aiming to provide an in-depth characterization of the microbial communities associated with OSA.

A comprehensive literature search across PubMed, the Cochrane Library, Web of Science, and Embase databases were conducted to include studies published prior to Dec 2024 that compared the gut, respiratory and oral microbiota between individuals with and without OSA. The findings regarding alpha-diversity, beta-diversity, and relative abundance of microbiota extracted from the included studies were summarized. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the study protocol was registered with PROSPERO (CRD42024525114).

We identified a total of 753 articles, out of which 27 studies were ultimately included in the systematic review, involving 1,381 patients with OSA and 692 non-OSA populations, including 1,215 OSA patients and 537 non-OSA populations in adults and 166 OSA patients and 155 non-OSA populations in children. The results of alpha diversity revealed a reduction in the Chao1 index (SMD = -0.40, 95% CI = -0.76 to -0.05), Observed species (SMD = -0.50, 95% CI = -0.89 to -0.12) and Shannon index (SMD = -0.27, 95% CI = -0.47 to -0.08) of the gut microbiota in patients with OSA. Beta diversity analysis indicated significant differences in the gut, respiratory and oral microbial community structure between individuals with OSA and those without in more than half of the included studies. Furthermore, in comparison to the non-OSA individuals, the gut environment of patients with OSA exhibited an increased relative abundance of phylum Firmicutes, along with elevated levels of genera Lachnospira; conversely, there was a decreased relative abundance of phylum Bacteroidetes and genus Ruminococcus and Faecalibacterium. Similarly, within the oral environment of OSA patients, there was an elevated relative abundance of phylum Actinobacteria and genera Neisseria, Rothia, and Actinomyces.

Patients with OSA exhibit reduced diversity, changes in bacterial abundance, and altered structure in the microbiota, especially in the gut microbiota. The results of this study provide basic evidence for further exploration of microbiome diagnostic markers and potential intervention strategies for OSA.

Over the past 2 decades, the gut microbiota has emerged as a key player in human health, being involved in many different clinical contexts. Yet, many aspects of the relationship with its host are poorly documented. One obstacle is the substantial variability in wet-laboratory procedures and data processing implemented during gut microbiota studies, which poses a challenge of comparability and potential meta-analysis.

The study protocol described here aimed to better understand the relationship between health, dietary habits, and the observed heterogeneity of gut microbiota composition in the general population. "Le French Gut - Le microbiote français" aimed to collect, sequence, and analyze 100,000 fecal samples from French residents using a high-quality shotgun metagenomic pipeline, complemented with comprehensive health, lifestyle, and dietary metadata.

"Le French Gut - Le microbiote français" is a prospective, noninterventional French national study involving individuals, the creation of a biological collection (feces), and the exploitation of data from questionnaires and the National Health Data System (Système National des Données de Santé). This national study is open to all metropolitan French adult residents, excluding those who have undergone a colectomy or digestive stoma, or who have had a colonoscopy or taken antibiotics in the last 3 months. This is a home-based trial in which volunteers complete a questionnaire with insights about their health and habits, and in which stool samples are self-collected. Data analysis is structured into 6 work packages, each focusing on a specific aspect of the gut microbiome, including its composition and associations with lifestyle, quality of life, and health.

This paper outlines the study protocol, with recruitment having started in September 2022 and expected to continue until the end of December 2025. As of January 2025, a total of 20,000 participants have been enrolled. The first scientific publications based on the data analysis are expected by mid-2025.

"Le French Gut" aims to provide a reference database and new ecosystem tools for understanding the relationship between the gut microbiota, its host, and diet. We expect to be able to find new signatures or targets and promote the design of innovative preventive strategies, personalized nutrition, and precision medicine.

ClinicalTrials.gov NCT05758961; https://clinicaltrials.gov/study/NCT05758961.

DERR1-10.2196/64894.

Insomnia with objective short sleep duration is associated with increased hypertension risk. We aimed to explore the mechanism underlying the association between objective short sleep duration and hypertension in patients with chronic insomnia disorder (CID) by multi-omics.

CID was defined according to International Classification of Sleep Disorders-3, and objective short sleep duration was based on the median value of total sleep time of the overall subjects during an overnight polysomnography. We used the mean values of measured nighttime and morning systolic (SBP) and diastolic blood pressure (DBP) for analysis. Serum metabolomics and fecal 16S rDNA amplicon sequencing were used to explore characteristic metabolites and analyze gut microbiota distribution, respectively.

One hundred and three patients with CID and 70 normal sleepers were included. We found 52 objective short sleep duration insomnia phenotype (ISSD)-related serum metabolites. Among the 52 ISSD-related serum metabolites, indoxyl sulfate was positively correlated with BP after adjusting for confounding factors (SBP: β = 0.250, p = .028; DBP: β = 0.256, p = .030) in ISSD. In addition, the level of serum indoxyl sulfate was significantly correlated with the genera Prevotella 9 (r = .378, p = .027), CAG-56 (r = -.359, p = .037), Ruminiclostridium 9 (r = -.340, p = .049), and Ruminococcus 2 (r = -.356, p = .039) in ISSD.

Our study suggests that the ISSD phenotype is associated with significant changes in serum metabolic profile, including high levels of indoxyl sulfate. The latter molecule correlates both with BP and gut microbiota in patients with the ISSD phenotype, suggesting that indoxyl sulfate may be the molecular path resulting in increased hypertension risk in this phenotype.

Specific antiretroviral therapy (ART) regimens are associated with weight gain in people living with HIV (PLWH). Gut microbiota is involved in weight gain in humans and animals. Human gut microbiota can be classified into enterotypes with distinct microbial and functional profiles.

In a cohort of 118 PLWH, we analyzed the gut microbiome in relation to weight gain and ART regimen using 16S rRNA gene sequencing, taking enterotype classification into account.

The enterotype was strongly associated with sexual orientation. Of the 67 individuals forming a Prevotella-dominated enterotype cluster in principal coordinates analysis, 93% were men who had sex with men (MSM), while 31% of individuals in the Bacteroides-dominated enterotype cluster were MSM and 69% were non-MSM. Forty-nine genera differed significantly between the MSM and non-MSM individuals. When stratified by dominant genus, only six taxa were associated with weight gain. Of these, five were restricted to Bacteroides-dominated individuals. Among them, the class Actinobacteria and genus Bifidobacterium differed between individuals gaining more than 5% weight and less than 5% weight 1 year after ART switch. Additionally, three taxa were significantly different between 15% of individuals with the highest weight gain (≥6.3%) and the highest weight loss (≤3.19%) 1 year after ART switch, including the phyla Firmicutes, Verrucomicrobia, and Synergistetes. Distinct functional properties in Bacteroides, but not Prevotella-dominated enterotype individuals, linked to weight gain were observed, particularly for glycan and lipid metabolism. Additionally, ART regimen-associated differences were observed for the phylum Actinobacteria, although this was limited to Prevotella-dominated enterotype individuals.

Differences in the composition and functional characteristics of the gut microbiome associated with weight gain and ART regimens were enterotype-specific and relatively small compared with differences linked to sexual orientation. Due to the substantial differences in gut microbiome structure among many MSM, categorization into enterotypes is useful for identifying differences in microbiome composition associated with variables such as weight gain or ART, which may be limited to a single enterotype. This may further advance the identification of microbes that contribute to weight gain or alter the gut microbiome composition in the context of the enterotype.