The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.

Resveratrol (RSV), a natural polyphenol, has been suggested to influence glucose and lipid metabolism. However, the underlying molecular mechanism of its action remains largely unknown due to its multiple biological targets and low bioavailability. In this study, we demonstrate that RSV supplementation ameliorates high-fat-diet (HFD)-induced gut microbiota dysbiosis, enhancing the abundance of anti-obesity bacterial strains such as Akkermansia, Bacteroides and Blautia. The critical role of gut microbiota in RSV-mediated anti-obesity effects was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation (FMT), which showed that RSV treatment effectively mitigates body weight, histopathological damage, glucose dysregulation and systematic inflammation associated with HFD. Metabolomics analysis revealed that RSV supplementation significantly increases the levels of the gut microbial flavonoid catabolite 4-hydroxyphenylacetic acid (4-HPA). Notably, 4-HPA was sufficient to reverse obesity and glucose intolerance in HFD-fed mice. Mechanistically,4-HPA treatment markedly regulates SIRT1 signaling pathways and induces the expression of beige fat and thermogenesis-specific markers in white adipose tissue (WAT). These beneficial effects of 4-HPA are partially abolished by EX527, a known SIRT1 inhibitor. Collectively, our findings indicate that RSV improve obesity through a gut microbiota-derived 4-HPA-SIRT1 axis, highlighting gut microbiota metabolites as a promising target for obesity prevention.

Previous studies have shown changes in gut microbiota after human immunodeficiency virus (HIV) infection, but there is limited research linking the gut microbiota of people living with HIV (PLWHIV) to metabolic diseases.

A total of 103 PLWHIV were followed for 48 weeks of anti-retroviral therapy (ART), with demographic and clinical data collected. Gut microbiome analysis was conducted using metagenomic sequencing of fecal samples from 12 individuals. Nonalcoholic fatty liver disease (NAFLD) was diagnosed based on controlled attenuation parameter (CAP) values of 238 dB/m from liver fibro-scans. Participants were divided based on the presence of metabolic disorders, including NAFLD, overweight, and hyperlipidemia. Akkermansia abundance in stool samples was measured using RT-qPCR, and Pearson correlation and logistic regression were applied for analysis.

Metagenomic sequencing revealed a significant decline in gut Akkermansia abundance in PLWHIV with NAFLD. STAMP analysis of public datasets confirmed this decline after HIV infection, while KEGG pathway analysis identified enrichment of metabolism-related genes. A prospective cohort study with 103 PLWHIV followed for 48 weeks validated these findings. Akkermansia abundance was significantly lower in participants with NAFLD, overweight, and hyperlipidemia at baseline, and it emerged as an independent predictor of NAFLD and overweight. Negative correlations were observed between Akkermansia abundance and both CAP values and body mass index (BMI) at baseline and at week 48. At the 48-week follow-up, Akkermansia remained a predictive marker for NAFLD.

Akkermansia abundance was reduced in PLWHIV with metabolic disorders and served as a predictive biomarker for NAFLD progression over 48 weeks of ART.

Sarcopenic obesity is a multifactorial disorder commonly found in elderly individuals. One contributing factor is gut microbiota dysbiosis. This study compared the abundance of certain bacteria in elderly individuals with obesity and sarcopenic obesity.

The study included 50 elderly individuals over 65 with a body mass index (BMI) of over 30 kg/m², both sexes. Participants were divided into two groups, each with 25 individuals, based on the diagnosis of sarcopenia using the EWGSOP2 criteria. Individuals with underlying diseases, those using antibiotics, and those with a history of gastrointestinal surgery were excluded. Stool samples were stored at -80 °C, and DNA was extracted using standard kits. Bacterial DNA sample quality was assessed using a Nanodrop device. Bacterial frequency was measured using qPCR. The log cfu for each bacteria was calculated and compared in both groups using an independent t-test. Spearman measured the correlation between bacterial genera and physical performance in SPSS 26.

The case group had a significantly higher average age (70.96) than the control group (68.32). The average BMI was the same in both groups. The frequency of Escherichia (p-value = 0.046) and Bifidobacterium (p-value = 0.017) was significantly higher in the case group. There was no significant difference in the frequency of Lactobacillus and Akkermansia.

The study uncovered substantial differences in gut microbiota composition between elderly individuals experiencing sarcopenic obesity and those with obesity alone. The findings suggest that dysbiosis, characterized by an excessive presence of Bifidobacterium, Escherichia, and Akkermansia, may be associated with sarcopenic obesity.

The online version contains supplementary material available at 10.1007/s40200-025-01584-x.

Overweight and obesity have been associated with an altered intestinal microbiome. Recent investigations have demonstrated that fiber supplementation, including chitosan, can exert beneficial and protective effects on the composition of gut microbiota in humans diagnosed with overweight/obesity. However, there is still a great deal of heated debate regarding the impact of chitosan supplementation in overweight and obese adolescents. Therefore, the aim of this study is to clarify the effects of chitosan administration on the composition of the gut microbiome in overweight and obese adolescents.

Sixty-four overweight and obese adolescents were subjected to supplementation with 3 g of chitosan for 12 weeks. Anthropometric indices and physical activity were measured at the beginning and at the end of the intervention. After DNA extraction and purification, the quantity of bacteria in the patients' stool samples was determined by real-time polymerase chain reaction (PCR). The RCT was registered on the Iranian Registry of Clinical Trials ( www.irct.ir ) website (IRCT20091114002709 N57; registration date: 2021 - 06 - 20).

Individuals who received chitosan supplementation experienced a significant decrease in the BMI z-score (P < 0.001). Administration of chitosan led to notable significant decrease in the Firmicutes (P < 0.001) populations and the ratio of Firmicutes to Bacteroidetes (P < 0.001) as well as a notable increase in the Bacteroidetes (P = 0.008) and Akkermansia (P < 0.001) populations, respectively compare to control group. Mean changes in Lactobacillus populations were marginally significant (P = 0.05). Chitosan administration did not alter the composition in Bifidobacterium populations (P = 0.97).

The present study demonstrates beneficial effects of chitosan administration on some bacterial species associated with overweight and obesity in adolescents. Further research is needed to confirm our findings and clarify the impact of this intervention on the Lactobacillus population in the gut.

Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota.

We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor's sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity.

Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had microbiotas that were highly perturbed by CMC exposure in the MBRA model. CMC-induced microbiota perturbability was associated with a baseline metagenomic signature, suggesting the possibility of using one's metagenome to predict sensitivity to dietary emulsifiers. Transplant of human microbiotas that the MBRA model deemed CMC-sensitive, but not those deemed insensitive, into IL-10-/- germfree mice resulted in overt colitis following CMC feeding.

These results suggest that an individual's sensitivity to emulsifier is a consequence of, and can thus be predicted by, examining their baseline microbiota, paving the way to microbiota-based personalised nutrition.

Mucins, heavily O-glycosylated glycoproteins, are a key component of mucus, and certain gut microbiota, including Akkermansia muciniphila, can utilise mucin glycans as a carbon source. Akkermansia muciniphila produces the O-glycopeptidase enzyme OgpA, which cleaves peptide bonds at the N-terminus of serine (Ser) or threonine (Thr) residues carrying O-glycan substitutions, with selectivity influenced by the O-glycan functional groups. Using molecular dynamics (MD) simulations and quantum chemistry calculations, we explored how different O-glycan groups affect OgpA's selectivity. Our results show that peptides bind to the enzyme via hydrogen bonds, π-π interactions, van der Waals forces and electrostatic interactions, with key residues, including Tyr90, Val138, Gly176, Tyr210 and Glu91, playing important roles. The primary determinant of selectivity is the interaction between the peptide's functional group and the enzyme's binding cavity, while peptide-enzyme interface interactions are secondary. Quantum chemistry calculations reveal that OgpA prefers peptides with a lower electrophilic character. This study provides new insights into mucin degradation by gut microbiota enzymes, advancing our understanding of this critical biological process.

Diabetes Mellitus (DM) is a metabolic disease that manifests as a state of "chronic low-grade inflammation". Patients with DM have a disorder of intestinal flora. There is a discernible correlation between this disorder of intestinal flora and the onset and progression of eye diseases, which offers novel insights into treating eye diseases through the modulation of intestinal flora. Here, we demonstrated that a high-fat diet and streptozotocin injection-induced intestinal microbiota dysbiosis can lead to dry eye-like manifestations in T2DM mice. Probiotic and prebiotic treatments not only alleviated intestinal inflammation and barrier disruption, but also mitigated damage to the lacrimal barrier and suppressed immune cell infiltration and inflammatory responses. Additional mechanism investigation found that probiotics and prebiotics inhibited the TLR4/NF-κB signaling pathway and its downstream pro-inflammatory products both in the lacrimal gland and colon. 16S RNA sequencing identified a reduction in the bacterial genera Akkermansia and Lactobacillus in the fecal samples of DM mice. By contrast, treatment with probiotics and prebiotics led to a reshaping of the intestinal microbial community and a reduction in bile acid metabolites, such as taurocholic acid and deoxycholic acid. Our current study demonstrates that probiotic and prebiotic treatments can ameliorate dry eye-like symptoms and associated pathological changes in T2DM mice. Moreover, we proved that a high-fat diet and STZ-induced microbiota dysbiosis were involved in diabetic dry eye through the gut-eye axis.

The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.

Effective, user-friendly, lifestyle-compatible, and economic treatment for type 2 diabetes (T2D) is urgently needed due to its high incidence and health threats. Here, we remolded Lactococcus lactis through genetic engineering to persistently secrete glucagon-like peptide-1 (L. lactis-GLP-1) and subsequent bioorthogonal arming with dopamine (DA)-based "gripper" and β-glucan (GN)-based "shield" (L. lactis-GLP-1-DA@GN) for treatment of T2D mice via oral administration. With protection by GN-based "shield", L. lactis-GLP-1-DA@GN achieved an impressive enhancement of survival by 20666 times compared with bare L. lactis-GLP-1 after experiencing gastrointestinal conditions and DA-based "gripper" was shielded from interaction with the upper digestive tract. Once prebiotic GN was metabolized by gut microbiota into short-chain fatty acids (SCFAs), underlying DA-based "gripper" was exposed to assist intestinal colonization of L. lactis-GLP-1, achieving synergistic treatment effects through secreted GLP-1 and SCFAs. With all advances, oral administration of L. lactis-GLP-1-DA@GN realized effective T2D treatment through improving glucose/lipid homeostasis, repairing major organs' damages, and positively modulating gut microbiota. Moreover, multi-omics analysis revealed that L. lactis-GLP-1-DA@GN also mainly intervened in liver's signaling pathways regarding lipid metabolism and oxidative regulation to advance anti-T2D process. Our strategy marks reconstruction of probiotics by combining chemical and biological tools, broadening the avenue of manipulating probiotics for disease treatments.

The human body is habitat to a wide spectrum of microbial populations known as microbiota, which play an important role in overall health. The considerable research has mostly focused on the gut microbiota due to its potential to impact numerous physiological functions and its correlation with a variety of disorders, such as cardiovascular diseases (CVDs). Imbalances in the gut microbiota, known as dysbiosis, have been linked to the development and progression of CVDs through various processes, including the generation of metabolites like trimethylamine-N-oxide and short-chain fatty acids. Studies have also looked at the idea of using therapeutic interventions, like changing your diet, taking probiotics or prebiotics, or even fecal microbiota transplantation (FMT), to change the gut microbiota's make-up and how it works in order to prevent or treat CVDs. Exploring the cause-and-effect connection between the gut microbiota and CVDs offers a hopeful path for creating innovative microbiome-centered strategies to prevent and cure CVDs. This review presents an in-depth review of the correlation between the gut microbiota and CVDs, as well as potential therapeutic approaches for manipulating the gut microbiota to enhance cardiovascular health.

In the current era, metabolic dysfunction-associated steatotic liver disease (MASLD) has gradually developed into a major type of chronic liver disease that is widespread globally. Numerous studies have shown that the gut microbiota plays a crucial and indispensable role in the progression of MASLD. Currently, the gut microbiota has become one of the important entry points for the research of this disease. Therefore, the aim of this review is to elaborate on the further associations between the gut microbiota and MASLD, including the changes and differences in the microbiota between the healthy liver and the diseased liver. Meanwhile, considering that metabolic dysfunction-associated fatty liver and metabolic dysfunction-associated steatohepatitis are abnormal pathological states in the development of the disease and that the liver exhibits different degrees of fibrosis (such as mild fibrosis and severe fibrosis) during the disease progression, we also conduct a comparison of the microbiota in these states and use them as markers of disease progression. It reveals the changes in the production and action mechanisms of short-chain fatty acids and bile acids brought about by changes in the gut microbiota, and the impact of lipopolysaccharide from Gram-negative bacteria on the disease. In addition, the regulation of the gut microbiota in disease and the production and inhibition of related disease factors by the use of probiotics (including new-generation probiotics) will be explored, which will help to monitor the disease progression of patients with different gut microbiota compositions in the future and carry out personalized targeted therapies for the gut microbiota. This will achieve important progress in preventing and combating this disease.

This study aims to investigate the immunomodulatory potential of Akkermansia muciniphila in restoring Porphyromonas gingivalis-induced immune dysfunction.

The immune response was assessed by measuring the expression of pro-inflammatory cytokines and antibacterial peptides in human gingival epithelial cells and human gingival fibroblasts treated with A. muciniphila, P. gingivalis, or a combination of both. Activation of the NF-κB pathway was analyzed using immunofluorescent staining and western blot. In vivo validation was performed using a mouse model, where A. muciniphila and P. gingivalis were administered alongside a MyD88-specific inhibitor to confirm the immunomodulatory mechanisms.

A. muciniphila significantly enhanced the defensive immune response through TLR-MYD88-NF-κB pathway. In vitro and in vivo, A. muciniphila upregulated chemokine expression to recruit immune cells. A. muciniphila also reduced the adhesion and internalization of P. gingivalis and increased the expression of genes encoding antimicrobial peptides (DEFB103B and CAMP).

A. muciniphila demonstrates potential in combating P. gingivalis infection highlighting its role as a promising immune modulator for periodontal disease management.

Yi Mai granule (YMG) is a traditional Chinese medicine (TCM) herbal decoction consisting of two TCM formulas: Gua-Lou-Ban-Xia decoction and Si-Jun-Zi decoction. YMG has shown clinical benefit in the treatment of nonalcoholic fatty liver disease (NAFLD), which may be due to its regulatory effects on lipid metabolism. Previous studies have highlighted the importance of the gut microbiota and its metabolites in the use of TCM. However, the effect of YMG on the gut microbiota in the treatment of NAFLD remains unclear. In this study, we established an NAFLD model in ApoE-/- mice and treated them with YMG. High-performance liquid chromatography was adopted to identify the chemical components of YMG. By mapping the candidate targets using network pharmacology, we found that the targets of the main components of YMG were significantly enriched in NAFLD-related pathways. Moreover, 16S rRNA gene sequencing revealed that YMG affected the constitution and metabolism of the gut microbiota in NAFLD model mice, including lipid and carbohydrate metabolism. Similarly, metabolites related to lipid and carbohydrate metabolism in mouse serum were significantly altered by YMG. The correlation heat map and network analyses showed that the gut microbiota and metabolites affected by YMG were closely related to the blood lipid content. Collectively, YMG may exert therapeutic effects by affecting the metabolism of gut microbiota, thus regulating lipid and carbohydrate metabolism. These findings offer novel insight into the pharmacological mechanism of YMG in the treatment of NAFLD and provide theoretical bases for its clinical applications.

Although the gut microbiota is known to act as a bridge between dietary nutrients and the body's energy needs, the interactions between the gut microbiota, host energy metabolism, and exercise capacity remain uncertain. Here, we characterized the gut microbiota ecosystem in a cohort of healthy normo-weight humans with highly heterogeneous aerobic exercise capacities and closely related body composition and food habits. While our data support the idea that the bacterial ecosystem appears to be modestly altered between individuals with low-to-high exercise capacities and close food habits, we report that gut bacterial α diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using fecal microbiota transplantation, we report that the engraftment of gut microbiota from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen stores into transplanted mice, which highlights promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity traits.

Alzheimer's disease (AD) is a progressive and chronic neurodegenerative disorder of the central nervous system, characterized by behavioral and dysexecutive deficits. Its pathogenesis is closely associated with the intestinal flora. This study aimed to explore the enterotypes in AD by identifying key bacteria through machine learning and species co-occurrence network analysis.

The collection of fecal samples from AD patients was followed by 16 S rRNA analysis using QIIME2. Enterotype clustering was conducted at the genus level, and deep neural network (DNN) classification models were developed for AD and healthy controls within each enterotype.

Analysis of three 16 S rRNA gut microbiome datasets identified three distinct enterotypes: Escherichia_Shigella (ET-E), Faecalibacterium (ET-F), and Bacteroides (ET-B). The ET-E is mainly characterized by the absence of Akkermansia in AD group. The Akkermansia was significantly positively correlated with Eubacterium_coprostanoligenes_group and negatively correlated with biosynthesis and amino acid metabolism. The ET-F highly expressed Agathobacter, un_f__Lachnospiraceae, Lachnoclostridium, and low expressed Dorea in AD group. Among them, Agathobacter was significantly positively correlated with un_f__Lachnospiraceae, and un_f__Lachnospiraceae was significantly positively correlated with Lachnoclostridium. The Dorea was significantly negatively correlated with Lachnoclostridium. The AD from ET-B group had high expression of two beneficial bacteria, Butyricicoccus and Parabacteroides. The findings suggest that the ET-E enterotype may predispose individuals to AD, with Akkermansia identified as a potential risk factor. Conversely, the ET-B enterotype appears to be associated with milder symptoms, with Butyricicoccus and Parabacteroides potentially serving as protective factors. Therefore, a comprehensive understanding of the species characteristics and interactions within different enterotypes is essential for modulating the gut-brain axis and mitigating AD symptoms.

Deciphering the gastrointestinal microbial response to oral SS DNA vaccines with different doses is helpful for identifying the mechanism for effective utilization of the vaccine for improving animal production. Here, we conduct a comparative study with different doses of vaccine (control: empty plasmid; low dose: 1 × 107 CFU vaccine; high dose: 1 × 1012 CFU vaccine) using goat as a case to investigate the potential of somatostatin vaccination from the entire gastrointestinal microbiota perspective. Our results show that body weight gain and slaughter rate are greater in the L_SS group than in the C_SS group. Compared with the C_SS group, the GH concentration is reduced, while the SS concentration is elevated in the cecum of L_SS goats. Moreover, the SCFAs concentration is elevated in the L_SS goats, the acetate molar proportion is lower in the rumen, the proportion of the acetate is decreased, and propionate is increased in the cecum of L_SS goats. Our data indicate that the low-dose somatostatin vaccine possesses a more efficient improvement in the productivity of goats, emphasizing that the dosage should be considered to reach its optimal effect on the host. Moreover, we find that different doses of the SS vaccination select distinct microbial communities in the gastrointestinal tract. Beta diversity analysis shows a significant interaction. Microorganisms capable of converting nutrients, including Ruminococcacease, Butyrivibrio, Akkermansia, and Lachnospiraceae are enriched, altering the gastrointestinal fermentation response to SS DNA vaccination of ruminants. Moreover, the correlation analysis results revealing these biomarkers have a close association with the phenotypes of productivity. These results imply that somatostatin immunoneutralization might directly alter the gastrointestinal tract commensal bacterial structure, improving gastrointestinal homeostasis, and, thus, modifying the fermentability and effected hormone level to improve the productivity of goats. Our study extends the understanding of the somatostatin vaccine regulation of ruminants' growth through the entire gastrointestinal microbial perspective.

Akkermansia muciniphila (A. muciniphila), a critical bacterium within the gut microbiota, plays a key role in human health and immunomodulation. Since its identification in 2004, A. muciniphila has emerged as a significant agent in treating metabolic diseases, gastroenterological diseases, and tumor immunotherapy. Its rapid ascent in scientific translation underscores its importance in gut microbiome research. However, there has been a lack of visualization and analysis of the rapidly occurring commercialization in this field, which has critically hindered insights into the current knowledge structure and understanding of the cutting-edge of the discipline. This study employs the Web of Science Core Collection (WOSCC) and Innography platforms to provide the first comprehensive analysis of A. muciniphila's academic progresses and commercialization over the past two decades, highlighting its growing prominence in global health research. Our analysis delineates that, following the academic trajectory, the evolution of A. muciniphila patents from foundational research through to application development and maturity, with particular emphasis on its expansive potential in emerging fields, including gastroenterological disorders, non-alcoholic fatty liver disease, cancer immunotherapy, stress management, and neurodegenerative disease treatment. Concluding, A. muciniphila presents as a next-generation probiotic with vast implications for human health. Our findings provide essential insights for future research and product development, contributing to the advancement of this burgeoning field.

Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance. Both groups showed decreases in body weight and glycated hemoglobin (HbA1c), without significant between-group differences. In participants with low baseline A. muciniphila, AKK-WST01 supplementation showed high colonization efficiency and significant reductions in body weight, fat mass, and HbA1c, which were not found in the placebo group. However, AKK-WST01 supplementation showed poor colonization and no significant clinical improvements in participants with high baseline A. muciniphila. These findings were verified in germ-free mice receiving feces with low or high A. muciniphila. Our study indicates that metabolic benefits of A. muciniphila supplementation could depend on its baseline intestinal levels, supporting the potential for gut microbiota-guided probiotic supplementation. (ClinicalTrials.gov number, NCT04797442).

Bariatric surgery is the most long-term effective treatment option for severe obesity. The role of gut microbiome (GM) in either the development of obesity or in response to obesity management strategies has been a matter of debate. This study aims to compare the impact of two of the most popular procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (GB), on metabolic syndrome parameters and gut bacterial microbiome and in systemic immuno-inflammatory response.

A prospective observational study enrolled 24 patients with severe obesity, 14 underwent SG and 10 GB. Evaluations before (0 M) and 6 months (6 M) after surgical procedures included clinical and biochemical parameters, expression of 17 immuno-inflammatory genes in peripheral blood leukocytes, and assessment of gut microbiome profile using 16 s rRNA next-generation sequencing approach. Statistical significance was set to a p value < 0.05 with an FDR < 0.1.

A significant and similar decrease in weight-associated parameters and for most metabolic markers was achieved with both surgeries. Considering the gut microbiome in the whole study population, there was an increase in alpha diversity at family-level taxa. Beta diversity between SG and GB at 6 M showed near significant differences (p = 0.042) at genus levels. Analysis of the relative abundance of individual taxonomic groups highlighted differences between pre- and post-surgical treatment and between both approaches, namely, a higher representation of family Enterobacteriaceae and genera Veillonella and Enterobacteriaceae_unclassified after GB. Increased expression of immune-inflammatory genes was observed mainly for SG patients.

We conclude that SG and GB have similar clinical and metabolic outcomes but different impacts in the gut bacterial microbiome. Results also suggest reactivation of immune response after bariatric surgery.

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease) is a chronic liver disease affecting over a billion individuals worldwide. MASLD can gradually develop into more severe liver pathologies, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and liver malignancy. Notably, although being a global health problem, there are very limited therapeutic options against MASLD and its related diseases. While a thyroid hormone receptor agonist (resmetirom) is recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in MASLD and MASH incidence, it is urgent to develop novel and effective therapeutic strategies against these prevalent liver diseases. In this article, the pathogenic mechanisms of MASLD and MASH, including insulin resistance, dysregulated nuclear receptor signaling, and genetic risk factors (eg, patatin-like phospholipase domain-containing 3 and hydroxysteroid 17-β dehydrogenase-13), are introduced. Various therapeutic interventions against MASH are then explored, including approved medication (resmetirom), drugs that are currently in clinical trials (eg, glucagon-like peptide 1 receptor agonist, fibroblast growth factor 21 analog, and PPAR agonist), and those failed in previous trials (eg, obeticholic acid and stearoyl-CoA desaturase 1 antagonist). Moreover, given that the role of gut microbes in MASLD is increasingly acknowledged, alterations in the gut microbiota and microbial mechanisms in MASLD development are elucidated. Therapeutic approaches that target the gut microbiota (eg, dietary intervention and probiotics) against MASLD and related diseases are further explored. With better understanding of the multifaceted pathogenic mechanisms, the development of innovative therapeutics that target the root causes of MASLD and MASH is greatly facilitated. The possibility of alleviating MASH and achieving better patient outcomes is within reach. SIGNIFICANCE STATEMENT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, and it can progress to more severe pathologies, including steatohepatitis, cirrhosis, and liver cancer. Better understanding of the pathogenic mechanisms of these diseases has facilitated the development of innovative therapeutic strategies. Moreover, increasing evidence has illustrated the crucial role of gut microbiota in the pathogenesis of MASLD and related diseases. It may be clinically feasible to target gut microbes to alleviate MASLD in the future.

Recently, probiotics have been investigated as potential therapeutic agents for various diseases. Clinical studies using probiotics have been conducted in humans with impaired glucose tolerance and type 2 diabetes mellitus. Chronic inflammation plays a pivotal role in initiating insulin resistance in the pathogenesis of type 2 diabetes, leading to cardiovascular diseases. Intestinal dysfunction and inflammation have been postulated to trigger systemic chronic inflammation, and it is assumed that the suppression of inflammation in the intestine is the point of activity of probiotics. Therefore, in this review, among the randomised controlled trials that evaluated the effects of probiotics in patients with impaired glucose tolerance and type 2 diabetes, we selected trials that evaluated the indices of glycaemic control and inflammation-related markers. Some trials have shown that the probiotics administration improved glycaemic indices, such as HbA1c levels, and reduced C-reactive protein levels and proinflammatory cytokines, such as IL-6, in the blood, suggesting the suppression of inflammation. Two trials showed improvements in glycaemic indices, implying that they were mediated by IL-10, an anti-inflammatory cytokine. Although a correlation between the suppression of inflammation by probiotics and improvement in glycaemic control has not been documented, one trial revealed that glycaemic control worsened, accompanied by a decrease in anti-inflammatory cytokine levels, after probiotics were discontinued. Other studies have shown that probiotics can reduce blood endotoxin levels and increase intestinal mucin production. These findings suggest that probiotic administration has enormous potential to suppress chronic inflammation in metabolic disorders, leading to improved glycaemic control. Suppression of chronic inflammation has been speculated to prevent vascular diseases in type 2 diabetes.

Akkermansia muciniphila is a gut bacterium that colonizes the gut mucosa, has a role in maintaining gut health and shows promise for potential therapeutic applications. The discovery of A. muciniphila as an important member of our gut microbiome, occupying an extraordinary niche in the human gut, has led to new hypotheses on gut health, beneficial microorganisms and host-microbiota interactions. This microorganism has established a unique position in human microbiome research, similar to its role in the gut ecosystem. Its unique traits in using mucin sugars and mechanisms of action that can modify host health have made A. muciniphila a subject of enormous attention from multiple research fields. A. muciniphila is becoming a model organism studied for its ability to modulate human health and gut microbiome structure, leading to commercial products, a genetic model and possible probiotic formulations. This Review provides an overview of A. muciniphila and Akkermansia genus phylogeny, ecophysiology and diversity. Furthermore, the Review discusses perspectives on ecology, strategies for harnessing beneficial effects of A. muciniphila for human mucosal metabolic and gut health, and its potential as a biomarker for diagnostics and prognostics.

Ultra-processed foods (UPFs) have become a widely consumed food category in modern diets. However, their impact on gut health is raising increasing concerns. This review investigates how UPFs impact the gut microbiome and gut barrier, emphasizing gut dysbiosis and increased gut permeability. UPFs, characterized by a high content of synthetic additives and emulsifiers, and low fiber content, are associated with a decrease in microbial diversity, lower levels of beneficial bacteria like Akkermansia muciniphila and Faecalibacterium prausnitzii, and an increase in pro-inflammatory microorganisms. These alterations in the microbial community contribute to persistent inflammation, which is associated with various chronic disorders including metabolic syndrome, irritable bowel syndrome, type 2 diabetes, and colorectal cancer. In addition, UPFs may alter the gut-brain axis, potentially affecting cognitive function and mental health. Dietary modifications incorporating fiber, fermented foods, and probiotics can help mitigate the effects of UPFs. Furthermore, the public needs stricter regulations for banning UPFs, along with well-defined food labels. Further studies are necessary to elucidate the mechanisms connecting UPFs to gut dysbiosis and systemic illnesses, thereby informing evidence-based dietary guidelines.

To investigate the relationship between heart failure (HF) and gut microbiota-mediated energy metabolism, and to explore the role of Shenfu Injection in this process.

In this study, Adriamycin-induced chronic heart failure (CHF) rat model was used and randomly divided into the blank control group (Normal, n = 9), HF control group (Model, n = 12), Shenfu Injection treatment group (SFI, n = 9), and positive drug control group (TMZ, n = 9). The changes in gut microbiota structure were analyzed by 16S rRNA high-throughput sequencing, the content of short-chain fatty acids (SCFAs) was detected by targeted metabolomics technology, and cardiac function and energy metabolism-related indicators were evaluated.

Myocardial energy metabolism in HF rats was disordered, characterized by reduced fatty acid oxidation, enhanced anaerobic glycolysis of glucose, mitochondrial damage, and decreased ATP content; The gut microbiota of HF rats was imbalanced, with a reduction in beneficial bacteria, an increase in conditional pathogenic bacteria, and impaired intestinal barrier function; Both Shenfu Injection and trimetazidine improved myocardial energy metabolism and cardiac function, but Shenfu Injection was more significant in regulating gut microbiota and improving intestinal health; The production of SCFAs from the gut microbiota of HF rats increased, which may be closely related to myocardial energy metabolism; SCFAs-producing bacteria Akkermansia and Blautia played a key role in the development of HF, and their abundance was positively correlated with SCFAs content.

Shenfu Injection in treating HF may improve myocardial energy metabolism and intestinal health by regulating gut microbiota, especially the abundance of SCFAs-producing bacteria Akkermansia and Blautia, thereby exerting therapeutic effects. This provides theoretical support for treatment strategies based on gut microbiota.

In the context of pollution-free waste treatment, anaerobic fermentation liquid (AFL), a prominent by-product of biogas engineering, has emerged as a focal point in contemporary research. Concurrently, vitamin C, an active compound abundant in fruits and vegetables, possesses extensive application potential. The development of efficient extraction processes and the utilization of its biological activities have garnered significant attention from researchers. This study investigated the impact of AFL on the growth and vitamin C content of Bok choy through field trials of varying concentrations of AFL. The results indicated that the growth characteristics of Bok choy exhibited a concentration-dependent trend with increasing AFL dosage, with the highest yield observed in the AFL-2 group (8.43 kg/m2). Additionally, with the increase in the concentration of the AFL application, the vitamin C content in Bok choy exhibited a trend of initially increasing and then decreasing, reaching its highest value (70.83 mg/100 g) in the AFL-1 group. Furthermore, response surface methodology was employed to optimize the microwave-assisted organic solvent extraction process of vitamin C, revealing that the optimal conditions for microwave-assisted extraction using a 2% citric acid solution were as follows: a microwave power of 313 W, a microwave time of 1.3 min, and a liquid-to-solid ratio of 16.4:1 v/w, achieving a vitamin C extraction rate of 90.77%. Subsequent mechanistic studies on colitis repair demonstrated that the combination of vitamin C and allicin significantly enhanced the ability of intestinal microorganisms to ferment and degrade complex carbohydrates in colitis-afflicted mice, thereby alleviating intestinal inflammation, markedly reducing bacterial invasion signals on intestinal epithelial cells, and decreasing the risk of intestinal infection. This study provides a valuable perspective for the harmless utilization of agricultural waste, and provides a theoretical basis and technical support for the high-value utilization of natural active ingredients.

The onset of dental caries is associated with multiple factors, including oral microbiota, dietary sugars, the defensive mechanisms of saliva and teeth, oral hygiene practices, and socioeconomic factors. However, its relationship with the gut microbiota remains to be further explored. It remains crucial to establish a definitive causal link between the gut microbiota and the development of dental caries. This study aimed to investigate the causal relationship between gut microbiota and the risk of dental caries, focusing on identifying specific microbial communities potentially implicated in its pathogenesis. Gut microbiota data from genome-wide association studies (GWAS) conducted by the MiBioGen consortium were utilized as the exposure variable, with dental caries as the outcome variable. A Mendelian randomization (MR) approach was employed, leveraging comprehensive, publicly available GWAS summary data from European populations. The primary analytical method was the inverse variance weighted method, supplemented by additional techniques such as the weighted median model, MR-Egger, simple mode, and weighted mode, to ensure the robustness of the results. Heterogeneity was evaluated using Cochran Q test, and potential pleiotropy was assessed through MR-Egger regression. Sensitivity analyses were performed using the leave-one-out method to further validate the findings. The results revealed that a higher relative abundance of Christensenellaceae, FamilyXIII, Ruminococcaceae, and Senegalimassilia was associated with a reduced risk of dental caries. In contrast, a higher relative abundance of Erysipelotrichia, Erysipelotrichales, Pasteurellales, Erysipelotrichaceae, Pasteurellaceae, Methanobrevibacter, Roseburia, and Terrisporobacter was linked to an elevated risk of dental caries. This study provides compelling evidence for a causal relationship between gut microbiota and the development of dental caries, offering novel insights into the potential role of specific gut microbial communities in the pathogenesis of dental caries.

Red mold rice, fermented by Monascus spp., has been reported to modulate gut microbiota composition and improve metabolic health. Previous studies indicate that red mold rice can reduce cholesterol, inhibit hepatic lipid accumulation, and enhance bile acid excretion, while also altering gut microbiota under high-fat dietary conditions. However, it remains unclear whether these effects are directly due to Monascus-derived products modulating gut microbiota or are a consequence of improved metabolic health conditions, which indirectly influence gut microbiota. This study aimed to evaluate the effects of Monascus pilosus SWM 008 fermented red mold rice and its components-monascin, monascinol, ankaflavin, and polysaccharides-on gut microbiota and metabolic health in rats fed a normal diet. Over eight weeks, physiological, biochemical, and gut microbiota parameters were assessed. Results showed no significant changes in body weight or liver/kidney function, confirming safety. Gut microbiota analysis revealed that red mold rice, monascin, monascinol, and polysaccharides significantly altered gut microbiota composition by increasing the relative abundance of beneficial bacteria, such as Akkermansia muciniphila, Ligilactobacillus murinus, and Duncaniella dubosii. Functional predictions indicated enhanced vitamin K2 biosynthesis, nucleotide metabolism, and other metabolic pathways linked to improved gut health. In conclusion, Monascus pilosus SWM 008 fermented red mold rice demonstrated safety and beneficial effects, suggesting its potential as a functional food to maintain gut microbiota balance under normal dietary conditions.

The human microbiome plays a vital role in human health, mediated by the gut-brain axis, with a large diversity of functions and physiological benefits. The dynamics and mechanisms of meditations on oral and gut microbiome modulations are not well understood. This study investigates the short-term modulations of the gut and oral microbiome during an Arhatic Yoga meditation retreat as well as on the role of microbiome in improving well-being through a possible gut-brain axis.

A single-arm pilot clinical trial was conducted in a controlled environment during a 9-day intensive retreat of Arhatic Yoga meditation practices with vegetarian diet. Oral and fecal samples of 24 practitioners were collected at the start (Day0: T1), middle (Day3: T2), and end (Day9:T3) of the retreat. Targeted 16S rRNA gene amplicon sequencing was performed for both oral and gut samples. Functional pathway predictions was identified using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). DESeq2 was used to identify the differential abundant taxa. Various statistical analyses were performed to assess the significant changes in the data.

Our findings revealed that Arhatic Yoga meditation together with a vegetarian diet led to changes in the oral and gut microbiome profiles within the 9-day retreat. Oral microbiome profile showed a significant (p < 0.05) difference in the species richness and evenness at the end of study, while non-metric multidimensional scaling (NMDS) confirmed the shift in the gut microbiome profile of the practitioners by T2 timepoint, which was further supported by PERMANOVA analysis (p < 0.05). Health-benefiting microbes known to improve the gastrointestinal and gut-barrier functions, immune modulation, and gut-brain axis were enriched. Gut microbiome of both beginner and advanced Arhatic Yoga practitioners showed similar trends of convergence by the end of study. This implies a strong selection pressure by Arhatic Yoga meditation together with a vegetarian diet on the beneficial gut microbiome.

This pilot study demonstrates that Arhatic Yoga meditation practices combined with a vegetarian diet during a short intensive retreat resulted in enrichment of known health-promoting microbes. Such microbial consortia may be developed for potential health benefits and used as probiotics to improve the gastrointestinal and immune systems, as well as functions mediated by the gut-brain axis.

Study was submitted in https://clinicaltrials.gov/on28-02-2024 . Retrospective registered.

Altered gut microbiota has emerged as a major contributing factor to the etiology of chronic conditions in humans. Antibiotic exposure, historically dating back to the mass production of penicillin in the early 1940s, has been proposed as a primary contributor to the cumulative alteration of microbiota over generations. However, the mechanistic link between the antibiotics-altered microbiota and chronic conditions remains unclear.

In this study, we discovered that variants of the key beneficial gut microbe, Akkermansia muciniphila, were selected upon exposure to penicillin. These variants had mutations in the promoter of a TEM-type β-lactamase gene or pur genes encoding the de novo purine biosynthesis pathway, and they exhibited compromised abilities to mitigate host obesity in a murine model. Notably, variants of A. muciniphila are prevalent in the human microbiome worldwide.

These findings highlight a previously unknown mechanism through which antibiotics influence host health by affecting the beneficial capacities of the key gut microbes. Furthermore, the global prevalence of A. muciniphila variants raises the possibility that these variants contribute to global epidemics of chronic conditions, warranting further investigations in human populations. Video Abstract.

The rising prevalence of obesity and related metabolic disorders highlights the urgent need for innovative research approaches. Utilizing machine learning (ML) algorithms to predict obesity-associated gut microbiota and validating their efficacy with specific bacterial strains could significantly enhance obesity management strategies.

We leveraged gut microbiome data from 1,563 healthy individuals and 2,043 overweight patients sourced from the GMrepo database. We assessed the anti-obesity effects of Bifidobacterium pseudocatenulatum through experimentation with Caenorhabditis elegans and C3H10T1/2 cells.

Our analysis revealed a significant correlation between gut bacterial composition and body weight. The top 40 bacterial species were utilized to develop ML models, with XGBoost demonstrating the highest predictive accuracy. SHAP analysis indicated a negative association between the relative abundance of six bacterial species, including B. pseudocatenulatum, and body mass index (BMI). Furthermore, B. pseudocatenulatum was shown to reduce lipid accumulation in C. elegans and inhibit lipid differentiation in C3H10T1/2 cells.

Bifidobacterium pseudocatenulatum holds potential as a therapeutic agent for managing diet-induced obesity, underscoring its relevance in microbiome-based obesity research and intervention.

Akkermansia muciniphila, as a probiotic, is negatively linked to IBD, obesity, and T2DM. The aim of this study was to comprehensively assess the research status of Akkermansia muciniphila over the past decade and explore the relationships between this bacterium and various health-related aspects.

Tools VOSviewer, Bibliometrix, and CiteSpace were used to analyze various aspects including publication metrics, contributors, institutions, geography, journals, funding, and keywords.

Over the past decade, research on Akkermansia muciniphila has demonstrated a consistent annual growth in the number of publications, with a notable peak in 2021. China led in the number of publications, totaling 151, whereas the United States exhibited a higher centrality value. Among the 820 institutions involved in the research, the University of California (from the United States) and the Chinese Academy of Sciences (from China) occupied central positions. Willem M. De Vos ranked at the top, with 12 publications and 1,108 citations. The journal GUT, which had 5,125 citations and an Impact Factor of 23.0 in 2024, was the most highly cited. The most cited articles deepened the understanding of the bacterium's impact on human health, spanning from basic research to translational medicine. Thirty-nine high-frequency keywords were grouped into five clusters, illustrating Akkermansia muciniphila's associations with metabolic diseases, chronic kidney disease, the gut-brain axis, intestinal inflammation, and Bacteroidetes-Firmicutes shifts.

Given Akkermansia muciniphila's anti-inflammatory and gut-barrier-strengthening properties, it holds promise as a therapeutic for obesity, metabolic disorders, and inflammatory conditions. Therefore, future research should explore its potential further by conducting clinical trials, elucidating its mechanisms of action, and investigating its efficacy and safety in diverse patient populations.

Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared between lower vs. higher dairy consumption groups. Multivariable negative binomial regression models for panel data were used to estimate the incidence rate ratio and 95% confidence interval for bacterial counts and dairy consumption. False discovery rate-adjusted p values (q value) < 0.05 indicated statistical significance.

Higher total dairy and milk consumption and lower cheese consumption were associated with higher alpha microbial diversity (adjusted p values < 0.05). Higher total dairy and milk consumption was also associated with higher relative abundance of Faecalibacterium. Higher milk consumption was associated with higher relative abundance of Akkermansia. Higher total dairy and cheese consumption was associated with lower relative abundance of Bacteroides.

Dairy consumption may influence host health by modulating the structure and composition of the colonic adherent gut microbiota.

Obesity is a chronic disease characterized by an excess of fat mass. It is accompanied by a low-grade chronic systemic inflammation state that leads to numerous health disorders. To counteract this scenario, dietary-derived caloric restriction (CR) is the principal intervention for weight loss. Furthermore, probiotic supplementation has gained attention as a co-intervention to optimize weight loss and other health-related factors. As such, we aimed to verify the effect of CR with probiotic supplementation on the body composition, quality of life, sleep quality, anxiety, stress, and depression symptoms of adult men living with obesity.

The study is called the Clinical Study of Obesity and Intestinal Microbiota (ECOMI). It is a randomized, double-blind, placebo-controlled clinical trial involving two parallel groups of stable-weight adult men living with obesity. The inclusion criteria were male individuals aged 25-44 years, with body mass index (BMI) ranging from 30.0 to 39.99 kg/m2, and stable body mass over the preceding three months. Participants were randomly assigned to two groups: Caloric Restriction with Probiotic (CRPRO) and Caloric Restriction with Placebo (CRPLA). The achieved CR was 30 % of the total daily energy expenditure. Macronutrients were distributed as 50 % carbohydrates, 30 % lipids, and 20 % proteins. Probiotic supplementation was carried out using two sachets/day of 1 g, containing 1 × 109 Colony Forming Units (CFU) of each strain: Lactobacillus acidophilus NCFM, Lactobacillus rhamnosus HN001, Lactobacillus paracasei Lpc-37 and Bifidobacterium lactis HN019, totaling 8 billion CFU/day. CR and probiotic (or placebo) supplementation intervention lasted 12 weeks. Body composition and psychobiological-related parameters (e.g., sleep, anxiety, stress, and depression) were assessed at baseline and following 12 weeks of intervention. Data are presented as mean and 95 % confidence interval (CI) and mean difference (MD).

The present study applied the per protocol analysis. Thirty-three subjects were evaluated and randomized, but only data from 25 (CRPLA n = 12 vs CRPRO n = 13) participants were included in the final analysis. We verified that CR resulted in weight loss (p < 0.001; η2ρ = 0.754) in both CRPLA (MD: -6.30 kg; p < 0.001) and CRPRO (MD: -5.97 kg; p < 0.001), without differences between groups (p = 0.823; η2ρ = 0.002). Moreover, both CRPLA (MD: -4.83 kg; p < 0.001) and CRPRO (MD: -5.20 kg; p < 0.001) decreased body fat without difference between groups (p = 0.712; η2ρ = 0.006). Regarding obesity-related problems, only the corporeality dimension (p < 0.001; η2ρ = 0.474) in both CRPLA (p = 0.028) and CRPRO (p = 0.039) improved. World Health Organization Quality of Life (WHOQoL)-related dimensions were improved for perception (p < 0.001; η2ρ = 0.630), satisfaction (p < 0.001; η2ρ = 0.778), and psychological domain (p < 0.001; η2ρ = 0.567), without differences between groups. Moreover, sleep quality (p < 0.001; η2ρ = 0.522) improved in both groups, without differences between groups. Finally, anxiety (p = 0.013; η2ρ = 0.250) and depression (p = 0.003; η2ρ = 0.345) scores assessed via the Depression, Anxiety and Stress Scale-21 (DASS-21) and the Beck Depression Inventory (BDI-II) (p < 0.001; η2ρ = 0.448) improved only in the CRPRO group.

Probiotic supplementation did not enhance the effects of caloric restriction on body composition, QoL-, or sleep-related parameters. However, anxiety and depressive symptoms improved only in the CRPRO group, despite no differences between groups after 12 weeks. Further studies are needed to confirm these findings.

Obesity is a global health crisis linked to numerous chronic diseases. The gut microbiome plays a crucial role in human metabolism, and emerging evidence suggests that modulating the microbiome may offer novel therapeutic avenues for obesity management.

This systematic review aimed to assess the efficacy and safety of microbiome-targeted interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, in improving body composition, metabolic parameters, and inflammatory markers in overweight and obese adults.

A comprehensive search of PubMed, Scopus, and ScienceDirect was conducted to identify relevant studies published between 2005 and 2023. Included studies were assessed for methodological quality and risk of bias using the Cochrane Collaboration tool.

Body composition: Most studies demonstrated significant reductions in body weight, Body mass index, and body fat percentage.

Improvements were observed in lipid profiles (reduced cholesterol, triglycerides) and glucose metabolism (improved insulin sensitivity).

Significant reductions were observed in inflammatory markers such as Interleukins (IL-6, IL-8) and C-reactive protein.

Interventions generally led to shifts in microbial composition, with increases in beneficial bacteria such as Bifidobacterium and Lactobacillus.

Adverse events were generally minimal and limited.

This review provides strong evidence that microbiome-targeted interventions can effectively improve body composition, metabolic parameters, and inflammatory markers in individuals with obesity. Further research is needed to optimize intervention strategies, identify specific microbial targets, and translate these findings into effective clinical applications.

Osteoarthritis (OA) is one of the most common degenerative diseases, and the number of patients has been constantly increasing. Non-steroidal anti-inflammatory drugs, glucocorticosteroids, opioids, etc., and surgical procedures, e.g. arthroplasty, are among the most common methods of treatment. There are reasons to believe that the gut microbiome (GMB) may influence inflammatory processes occurring in the pathomechanism of OA. The inflammatory processes occurring in the intestines may lead to disruption of tight junctions and increased concentrations of pro-inflammatory cytokines, resulting in increased permeability of intestines, causing low-grade inflammation, including in the joints. Methods of altering the GMB composition to reduce the inflammatory and joint degenerative processes are known only to some extent, and long-term research is required. Osteoarthritis, a particularly well-known and very widespread disease due to the aging population, is characterized by moderate and local inflammation. It occurs due to the effects of biomechanical cartilage wear with damage of joint structures, primarily through degenerative processes. OA represents a therapeutic challenge, and any element that can influence its inhibition is highly sought after. Therefore, these methods seem to offer a promising additional approach to treatment.

Xylooligosaccharides (XOS) ameliorate insulin resistance (IR) in gestational diabetes mellitus (GDM) probably by propagating Akkermansia muciniphila (Akk). This study aimed to investigate the effects and mechanisms of XOS, Akk and combination on IR in GDM mice/pseudo-germ-free (PGF) mice. Female mice were fed with AIN-93 (n = 19) and high fat diet (HFD) (n = 206). After 4 weeks, HFD-fed mice were further allotted to HFD, GDM, GDM + XOS, GDM + Akk, GDM + XOS + Akk, GDM + PGF, GDM + PGF + XOS, GDM + PGF + Akk, and GDM + PGF + XOS + Akk groups (n ≥ 19). GDM was induced by intraperitoneally injecting streptozotocin and PGF was established by intragastrically administrating antibiotic cocktails. XOS (500 mg/kg·BW) or/and Akk (4 × 108 CFU) were gavaged once a day for 10 days. Fasting blood glucose (FBG), insulin, oral glucose tolerance test (OGTT) and insulin signaling pathway were determined. Gut microbiota were detected by 16S rRNA sequencing and absolute quantities of Akk by qRT-PCR. Intestinal tissues were stained by Hematoxylin-Eosin and Periodic acid-Schiff-Alcian blue staining. Occludin and Zonula occludens-1 (ZO-1) in intestine, Natural killer group 2 member D (NKG2D) on intestinal epithelial lymphocytes (IELs) and NKG2D ligands (NKG2DL) on intestinal epithelial cells (IECs) were detected by Western blotting. In GDM mice, XOS, Akk and XOS + Akk reduced (p < 0.05) the area under the curve of OGTT (AUC), insulin and homeostasis model assessment of insulin resistance (HOMA-IR), and increased (p < 0.05) protein kinase B (Akt) phosphorylation in liver and insulin receptor substrate 1 (IRS-1) phosphorylation in muscle. Furthermore, XOS + Akk reduced (p < 0.05) FBG and increased (p < 0.05) Akt phosphorylation in muscle and IRS-1 phosphorylation in liver. XOS, Akk and XOS + Akk reshaped gut microbiota with XOS + Akk exhibiting the greatest effectiveness. XOS increased (p < 0.05) Akk and clearance of gut microbiota abolished such effect. XOS, Akk and XOS + Akk reduced (p < 0.05) the small intestine Chiu's score and the colon Dieleman's scores, increased (p < 0.05) ZO-1 and Occludin, and reduced (p < 0.05) NKG2D on IELs and NKG2DLs (H60, MULT-1, Rae-1ε) on IECs. Moreover, XOS + Akk reduced (p < 0.05) MULT-1 in duodenum. Collectively, XOS and Akk synergistically ameliorate IR by reshaping gut microbiota, improving intestinal barrier and regulating NKG2D/NKG2DL signaling in GDM mice.

Akkermansia muciniphila is a bacterium commonly found in the human gastrointestinal tract that has received considerable interest as a potential probiotic for the improvement of gut health and overall metabolic function. A. muciniphila is enriched in the mucus layer of the intestinal lining, where it degrades mucin and plays a significant role in gut barrier maintenance and immune regulation. A higher abundance of A. muciniphila has been observed in the gut of healthy individuals relative to those with metabolic disorders, and multiple metabolic benefits, including improved glucose management, reduced body fat, and reduced inflammation have been linked to A. muciniphila. Current research on A. muciniphila primarily relies on mouse models, with limited human interventional studies available. While these animal studies offer valuable insights into the potential roles of A. muciniphila in health and disease, further clinical investigations in humans are needed to fully understand its impact. Here, we explore the current scope of A. muciniphila research and its potential as a therapeutic agent to improve gut and metabolic health while also emphasizing the need to optimize techniques to further improve studies of this organism.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic disorder of the liver and affects many people worldwide. Intestinal bacteria are thought to be involved in the pathological progression of NAFLD; therefore, improving the intestinal microbiota may be important in controlling NAFLD. In this study, we assessed the effects of water-soluble cellulose acetate (WSCA) on the intestinal microbiota in a non-alcoholic steatohepatitis (NASH) mouse model. Methods: NASH model (STAM mice) was created by streptozotocin injection and feeding the mice a high-fat diet. The serum biochemical parameters were analyzed. Intestinal bacterial populations were analyzed using paired-end sequencing of 16S rRNA, 18S rRNA, and internal transcribed spacer gene. Results: Our findings indicated that WSCA administration tends to improve the serum alanine aminotransferase and glucose levels in STAM mice and decreased the alpha diversity and altered the beta diversity of their intestinal microbiota. Additionally, WSCA intake resulted in an increase in the abundance of Coriobacteriaceae_UCG-002 and a decrease in the abundance of Enterobacter. Conclusions: WSCA intake can alter specific microbial compositions to improve blood glucose levels and liver functions and may improve the pathogenesis of NAFLD.