Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host's dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions.

Maternal diets during pregnancy and lactation are critical determinants that regulate the metabolic homeostasis in offspring. Our previous research demonstrated that maternal genistein (GEN) intervention ameliorated the dysregulation of glucolipid metabolism induced by intrauterine overnutrition in adult offspring, accompanied by changes in the composition of gut microbiota; however, the underlying mechanisms remain unclear. Here, we used a maternal overnutrition model induced by excess energy intake before and throughout pregnancy and lactation, with maternal GEN administered during the same period. The female offspring were raised on a standard chow diet until sacrificed at 24 weeks. The mRNA levels of browning markers were quantified in inguinal subcutaneous adipose tissues, followed by methylation analysis via the MassArray method. Cecal contents were collected for untargeted metabolomic analysis and a target quantitative analysis of methionine cycle metabolites. Spearman correlation analyses were used to assess whether cecal metabolites are involved in the methylation of browning-related genes and influence their expression. The results showed that maternal GEN supplementation reversed the downregulation of browning markers caused by perinatal high-fat diets in adult female offspring, consistent with a reduction in their methylation levels. Subsequently, we also found that maternal GEN consumption altered cecal metabolite profiles in offspring, promoting the production of bile acids, potent regulators of glucolipid metabolism, and reducing metabolites involved in the methionine cycle, key methyl donors for the methylation process. Furthermore, the abundances of these metabolites were significantly correlated with the methylation and expression levels of browning markers. Overall, this discovery suggested that maternal GEN intake decreased the methylation level of browning markers and induced browning in white adipose tissue of offspring, which correlated with alterations in cecal metabolites. We provide a novel theoretical basis for GEN as a promising nutritional supplement to break the vicious cycle of maternal metabolic disturbances being transmitted to offspring.

Homocysteine, a sulfur-containing amino acid, is an intermediate product during the metabolism of methionine, a vital amino acid. An elevated concentration of homocysteine in the plasma, named hyperhomocysteinemia, has been significantly related to the onset of several diseases, including diabetes, multiple sclerosis, osteoporosis, cancer, and neurodegenerative disorders such as dementia, Alzheimer's and Parkinson's diseases. An interaction between metabolic pathways of homocysteine and gut microbiota has been reported, and specific microbial signatures have been found in individuals experiencing hyperhomocysteinemia. Furthermore, some evidence suggests that gut microbial modulation may exert an influence on homocysteine levels and related disease progression. Conventional approaches for managing hyperhomocysteinemia typically involve dietary interventions alongside the administration of supplements such as B vitamins and betaine. The present review aims to synthesize recent advancements in understanding interventions targeted at mitigating hyperhomocysteinemia, with a particular emphasis on the role of gut microbiota in these strategies. The emerging therapeutic potential of gut microbiota has been reported for several diseases. Indeed, a better understanding of the complex interaction between microbial species and homocysteine metabolism may help in finding novel therapeutic strategies to counteract hyperhomocysteinemia.

Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression.

To investigate the relationship between Hcy, microbiome, and cognition in depressive patients.

We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function.

Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05).

Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.

Cardiometabolic disease is the leading cause of death in zoo apes; yet its etiology remains unknown. Here, we investigated compositional and functional microbial markers in fecal samples from 57 gorillas across U.S. zoos, 20 of which are diagnosed with cardiovascular disease, in contrast with 17 individuals from European zoos and 19 wild gorillas from Central Africa. Results show that zoo-housed gorillas in the U.S. exhibit the most diverse gut microbiomes and markers of increased protein and carbohydrate fermentation, at the expense of microbial metabolic traits associated with plant cell-wall degradation. Machine learning models identified unique microbial traits in U.S. gorillas with cardiometabolic distress; including reduced metabolism of sulfur-containing amino acids and hexoses, increased abundance of potential enteric pathogens, and low fecal butyrate and propionate production. These findings show that cardiometabolic disease in gorillas is potentially associated with altered gut microbial function, influenced by zoo-specific diets and environments.

Intestinal microbiota are pathophysiologically involved in diabetic nephropathy (DN). Dapagliflozin, recognized for its blood glucose-lowering effect, has demonstrated efficacy in improving DN. However, the mechanisms beyond glycemic control that mediate the impact of dapagliflozin on DN remain unclear. Here, we investigated the effects of dapagliflozin on DN and gut microbiota, elucidating how it mitigates DN via the gut-kidney axis. Low-dose dapagliflozin markedly ameliorated renal inflammation and fibrosis and improved gut barrier function in high-fat diet (HFD)/streptozotocin (STZ)-induced DN mice and db/db mice without affecting blood glucose levels. These effects were associated with altered gut microbial composition and function. Eradication of the resident microbiota abolished the protective effects of dapagliflozin against kidney injury in DN mice. Moreover, dapagliflozin significantly altered microbial metabolites in DN mice, decreasing argininosuccinic acid (ASA) and palmitic acid (PA), while increasing S-allylcysteine (SAC) levels. ASA and PA increased the expression of renal inflammation- and fibrosis-related markers in HK-2 cells, whereas SAC ameliorated renal damage and altered the microbial composition in a manner similar to dapagliflozin in DN mice. Notably, Muribaculaceae and Desulfovibrionaceae were correlated with the alleviation of DN-associated renal dysfunction by low- and high-dose dapagliflozin treatments in DN mice. These findings demonstrate a potential application of dapagliflozin in managing DN by targeting the gut microbiota.NEW & NOTEWORTHY We demonstrated that dapagliflozin administration alleviated renal inflammation and fibrosis in vivo and in vitro, along with reshaping the gut microbiota composition and altering levels of key microbial metabolites, including argininosuccinic acid (ASA) and palmitic acid (PA), while increasing S-allylcysteine (SAC). Importantly, the genera Muribaculaceae and Desulfovibrionaceae emerged as pivotal microbial genera mediating the protective effects of dapagliflozin against diabetic nephropathy.

Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host physiology via metabolites and structural components. A key mechanism is the modulation of host epigenetic pathways, especially histone modifications. An increasing number of studies indicate the role of the microbiota in regulating host circadian rhythms. However, the mechanisms remain largely unknown. Here, we summarize studies on microbial regulation of host circadian rhythms and epigenetic pathways, highlight recent findings on how the microbiota employs host epigenetic machinery to regulate circadian rhythms, and discuss its impacts on host physiology, particularly immune and metabolic functions. We further describe current challenges and resources that could facilitate research on microbiota-epigenetic-circadian rhythm interactions to advance our knowledge of circadian disorders and possible therapeutic avenues.

This review summarizes the intricate relationship between the microbiome and cancer initiation and development. Microbiome alterations impact metabolic pathways, immune responses, and gene expression, which can accelerate or mitigate cancer progression. We examine how dysbiosis affects tumor growth, metastasis, and treatment resistance. Additionally, we discuss the potential of microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, to modulate cancer metabolism. These interventions offer the possibility of reversing or controlling cancer progression, enhancing the efficacy of traditional treatments like chemotherapy and immunotherapy. Despite promising developments, challenges remain in identifying key microbial species and pathways and validating microbiome-targeted therapies through large-scale clinical trials. Nonetheless, the intersection of microbiome research and cancer initiation and development presents an exciting frontier for innovative therapies. This review offers a fresh perspective on cancer initiation and development by integrating microbiome insights, highlighting the potential for interdisciplinary research to enhance our understanding of cancer progression and treatment strategies.

The genetic diversity of the gut microbiota has a central role in host health. Here, we created pangenomes for 728 human gut prokaryotic species, quadrupling the genes of strain-specific genomes. Each of these species has a core set of a thousand genes, differing even between closely related species, and an accessory set of genes unique to the different strains. Functional analysis shows high strain variability associates with sporulation, whereas low variability is linked with antibiotic resistance. We further map the antibiotic resistome across the human gut population and find 237 cases of extreme resistance even to last-resort antibiotics, with a predominance among Enterobacteriaceae. Lastly, the presence of specific genes in the microbiota relates to host age and sex. Our study underscores the genetic complexity of the human gut microbiota, emphasizing its significant implications for host health. The pangenomes and antibiotic resistance map constitute a valuable resource for further research.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.

To comprehensively explore metabolomic changes in children with ASD, integrating findings from various research articles, reviews, systematic reviews, meta-analyses, case reports, editorials, and a book chapter.

A systematic search was conducted in electronic databases, including PubMed, PubMed Central, Cochrane Library, Embase, Web of Science, CINAHL, Scopus, LISA, and NLM catalog up until January 2024. Inclusion criteria encompassed research articles (83), review articles (145), meta-analyses (6), systematic reviews (6), case reports (2), editorials (2), and a book chapter (1) related to metabolomic changes in children with ASD. Exclusion criteria were applied to ensure the relevance and quality of included studies.

The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals. These metabolic biomarkers may serve as objective measures to support clinical assessments, improve diagnostic accuracy, and inform personalized treatment approaches. Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.

Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy, guiding personalized treatment approaches, monitoring treatment response, and improving outcomes. Further research is needed to validate findings, establish standardized protocols, and overcome technical challenges in metabolomic analysis. By advancing our understanding of metabolic dysregulations in ASD, clinicians can improve the lives of affected individuals and their families.

The involvement of the gut microbiota in anti-cancer treatment has gained increasing attention. Alterations to the structure and function of the gut bacteria are important factors in the development of cancer as well as the efficacy of chemotherapy. Recent studies have confirmed that the gut microbiota and related metabolites influence the pharmacological activity of chemotherapeutic agents through interactions with the immune system. This review aims to summarize the current knowledge of how malignant tumor and chemotherapy affect the gut microbiota, how the gut microbiota regulates host immune response, and how interactions between the gut microbiota and host immune response influence the efficacy of chemotherapy. Recent advances in strategies for increasing the efficiency of chemotherapy based on the gut microbiota are also described. Deciphering the complex homeostasis maintained by the gut microbiota and host immunity provides a solid scientific basis for bacterial intervention in chemotherapy.

The microbiota-gut-brain axis has been shown to play an important role in the stress response, but previous work has focused primarily on the role of the bacteriome. The gut virome constitutes a major portion of the microbiome, with bacteriophages having the potential to remodel bacteriome structure and activity. Here we use a mouse model of chronic social stress, and employ 16S rRNA and whole metagenomic sequencing on faecal pellets to determine how the virome is modulated by and contributes to the effects of stress. We found that chronic stress led to behavioural, immune and bacteriome alterations in mice that were associated with changes in the bacteriophage class Caudoviricetes and unassigned viral taxa. To determine whether these changes were causally related to stress-associated behavioural or physiological outcomes, we conducted a faecal virome transplant from mice before stress and autochthonously transferred it to mice undergoing chronic social stress. The transfer of the faecal virome protected against stress-associated behaviour sequelae and restored stress-induced changes in select circulating immune cell populations, cytokine release, bacteriome alterations and gene expression in the amygdala. These data provide evidence that the virome plays a role in the modulation of the microbiota-gut-brain axis during stress, indicating that these viral populations should be considered when designing future microbiome-directed therapies.

Due to their immediate exhalation after generation at the cellular/microbiome levels, exhaled volatile organic compounds (VOCs) may provide real-time information on pathophysiological mechanisms and the host response to infection. In recent years, the metabolic profiling of the most frequent respiratory infections has gained interest as it holds potential for the early, non-invasive detection of pathogens and the monitoring of disease progression and the response to therapy. Using previously unpublished data, randomly selected individuals from a COVID-19 test center were included in the study. Based on multiplex PCR results (non-SARS-CoV-2 respiratory pathogens), the breath profiles of 479 subjects with the presence or absence of flu-like symptoms were obtained using proton-transfer-reaction time-of-flight mass spectrometry. Among 223 individuals, one respiratory pathogen was detected in 171 cases, and more than one pathogen in 52 cases. A total of 256 subjects had negative PCR test results and had no symptoms. The exhaled VOC profiles were affected by the presence of Haemophilus influenzae, Streptococcus pneumoniae, and Rhinovirus. The endogenous ketone, short-chain fatty acid, organosulfur, aldehyde, and terpene concentrations changed, but only a few compounds exhibited concentration changes above inter-individual physiological variations. Based on the VOC origins, the observed concentration changes may be attributed to oxidative stress and antioxidative defense, energy metabolism, systemic microbial immune homeostasis, and inflammation. In contrast to previous studies with pre-selected patient groups, the results of this study demonstrate the broad inter-individual variations in VOC profiles in real-life screening conditions. As no unique infection markers exist, only concentration changes clearly above the mentioned variations can be regarded as indicative of infection or colonization.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent and challenging disease associated with a significant health and economic burden. MAFLD has been subjected to and widely investigated in many studies; however, the underlying pathogenesis and its progression have yet to understand fully. Furthermore, precise biomarkers for diagnosing and specific drugs for treatment are yet to be discovered. Increasing evidence has proven gut microbiota as the neglected endocrine organ that regulates homeostasis and immune response. Targeting gut microbiota is an essential strategy for metabolic diseases, including MAFLD. Gut microbiota in the gut-liver axis is connected through tight bidirectional links through the biliary tract, portal vein, and systemic circulation, producing gut microbiota metabolites. This review focuses on the specific correlation between gut microbiota metabolites and MAFLD. Gut microbiota metabolites are biologically active in the host and, through subsequent changes and biological activities, provide implications for MAFLD. Based on the review studies, gut-liver axis related-metabolites including short-chain fatty acids, bile acids (BAs), lipopolysaccharide, choline and its metabolites, indole and its derivates, branched-chain amino acids, and methionine cycle derivates was associated with MAFLD and could be promising MAFLD diagnosis biomarkers, as well as the targets for MAFLD new drug discovery.

This review explores the roles of methionine and arginine in promoting the well-being of poultry, with a specific focus on their impacts on intestinal and bone health. The metabolic pathways of methionine and arginine are elucidated, highlighting their distinct routes within the avian system. Beyond their fundamental importance in protein synthesis, methionine and arginine also exert their functional roles through their antioxidant capacities, immunomodulating effects, and involvement in the synthesis of metabolically important molecules such as S-adenosylmethionine, nitric oxide, and polyamines. These multifaceted actions enable methionine and arginine to influence various aspects of intestinal health such as maintaining the integrity of the intestinal barrier, regulating immune responses, and even influencing the composition of the gut microbiota. Additionally, they could play a pivotal role in promoting bone development and regulating bone remodeling, ultimately fostering optimal bone health. In conclusion, this review provides a comprehensive understanding of the potential roles of methionine and arginine in intestinal and bone health in poultry, thereby contributing to advancing the nutrition, overall health, and productivity of poultry in a sustainable manner.