Immunosuppression often leads to drastic metabolic, hormonal, and physiological disorders. Changes in the gut microbiota are believed to be one of the factors contributing to these disorders, but the association remains uncertain. Clinical studies can be complicated by confounding variables, such as diet and other drivers of heterogeneity in human microbiomes. In this study, we identified pronounced gut microbiome signatures in rhesus macaques (RMs) with immunosuppression-induced lipid metabolism disorders following cyclosporine combined with dexamethasone. Furthermore, we observed similar changes in the gut microbiota of mice with immunosuppression-induced lipid metabolism disorders, which were associated with short-chain fatty acid metabolism. ELISA showed that immunosuppression significantly reduced the levels of butyric acid in both feces and serum of mice. Spearman correlation analysis identified a significant correlation between serum butyric acid levels and gut microbial dysbiosis induced by immunosuppression, particularly in relation to f_Lachnospiraceae, g_unidentified_Ruminococcaceae, and s_Clostridium leptum. Additionally, mice transplanted with gut microbiota from immunosuppressed mice exhibited hepatic lipid metabolism disorders, and RNA sequencing revealed significant downregulation of ABC transporters and PPARα in the liver, which was closely associated with lipid transport and metabolism, particularly Abca1. Moreover, butyric acid supplementation alleviated hepatic lipid metabolism disorders and upregulated the expression of Abca1 and PPARα in mice transplanted with immunosuppression-induced gut microbiota. Thus, we propose that the combination of cyclosporine and dexamethasone regulates the expression of hepatic Abca1 and PPARα by modulating the gut microbiota and its derived butyrate, particularly Lachnospiraceae and Clostridium leptum, further regulating hepatic lipid metabolism.

This study investigated the longitudinal effects of acute (7-day) and prolonged (3-month) high-altitude exposure on gut microbiota in healthy adult males, addressing the limited data available in human populations. A cohort of 406 healthy adult males was followed, and fecal samples were collected at three time points: baseline at 800 m (406 samples), 7 days after ascending to 4,500 m (406 samples), and 2 weeks post-return to 800 m following 3 months at high altitude (186 samples). High-throughput 16S ribosomal DNA sequencing was employed to analyze microbiota composition and diversity. Results revealed significant changes in alpha- and beta-diversity, with acute high-altitude exposure inducing more pronounced effects compared to prolonged exposure. Specifically, acute exposure increased opportunistic pathogens (Ruminococcus and Oscillibacter) but decreased beneficial short-chain fatty acid producers (Faecalibacterium and Bifidobacterium). Notably, these changes in microbiota persisted even after returning to low altitude, indicating long-term remodeling. Functional analyses revealed substantial changes in metabolic pathways, suggesting microbiota-driven adaptations to energy utilization under high-altitude hypoxic conditions. In summary, acute high-altitude exposure caused dramatic changes in gut microbiota, while prolonged exposure led to structural and functional reshaping. These findings enhance our understanding of how high-altitude environments reshape gut microbiota.

This study is the first to investigate the impact of high-altitude exposure on gut microbiota adaptation in a large-scale longitudinal cohort. It seeks to enhance understanding of how high-altitude environments reshape gut microbiota. Acute exposure to high altitude significantly affected both α-diversity and β-diversity of gut microbiota, with acute exposure causing more pronounced changes than prolonged adaptation, indicating temporary disruptions in microbial communities. Notable shifts in microbial abundance were observed, including increased levels of genera linked to hypoxic stress (e.g., Gemmiger, Ruminococcus, and Parabacteroides) and decreased levels of beneficial bacteria (e.g., Faecalibacterium, Roseburia, and Bifidobacterium), suggesting possible adverse health effects. Functional analysis indicated changes in metabolism-related pathways post-exposure, supporting the idea that high-altitude adaptations involve metabolic adjustments for energy management. These findings enhance understanding of high-altitude physiology, illustrating the role of gut microbiota in hypoxic health.

Constipation is characterized by low frequent stools and difficult stool passage. Approximately 16% of the global population experiences these symptoms. Probiotics have shown promise in improving constipation symptoms by modulating the gut microbiome. This study aims to evaluate the effects of a probiotic formula (Lacto-5X) on bowel habits, gastrointestinal symptoms, gut microbiome, and metabolites in adults with mild constipation using a randomized, double-blind, placebo-controlled clinical trial design. At the 4-week endpoint, the Probiotic group had significant improvements in stool consistency, stool frequency, abdominal pain, and straining compared to the Placebo group. Satisfaction with bowel habits and improvement in overall intestinal health were significantly higher in the Probiotic group. Microbiome analysis revealed a significant increase in the abundance of Lactobacillus and L. plantarum in the Probiotic group at the 4-week endpoint. Metabolome analysis showed that L-proline level in the Probiotic group decreased, while threonic acid level increased at the 4-week endpoint compared to the Placebo group. However, these improvements were not sustained at the 8-week follow-up point. Lacto-5X changes the gut microbiome, leading to changes in metabolites, and it induced improved constipation symptoms. Continuous intake may be necessary to maintain these effects. Further studies are needed to explore the long-term efficacy of Lacto-5X.

The recent observational studies have unveiled the correlation between the composition and dynamic alterations of the gut microbiome and aging; however, the causal relationship remains uncertain.

The objective of this study is to investigate the causal relationship between the gut microbiome and accelerated aging as well as frailty, from a genetic perspective.

We obtained data on the gut microbiome, intrinsic epigenetic age acceleration, and Frailty Index from published large-scale genome-wide association studies. A two-sample Mendelian randomization analysis was conducted primarily using inverse variance weighting model. We utilized the MR-Egger intercept analysis, IVW method, the Cochran Q test, and the leave-one-out analysis to assess the robustness of the results.

IVW analysis indicated a potential association between Peptococcus (OR: 1.231, 95% CI 1.013-1.497, P = 0.037), Dialister (OR: 1.447, 95% CI 1.078-1.941, P = 0.014) and Subdoligranulum (OR: 1.538, 95% CI 1.047-2.257, P = 0.028) with intrinsic epigenetic age acceleration; while Prevotella 7 (OR: 0.792, 95% CI 0.672-0.935, P = 0.006) was associated with a potential protective effect. Allisonella (OR: 1.033, 95% CI 1.005-1.063, P = 0.022), Howardella (OR: 1.026, 95% CI 1.002-1.050, P = 0.031) and Eubacterium coprostanoligenes (OR: 1.037, 95% CI 1.001-1.073, P = 0.042) were associated with an increased risk of frailty; conversely, Flavonifractor (OR: 0.954, 95% CI 0.920-0.990, P = 0.012) and Victivallis (OR: 0.984, 95% CI 0.968-1.000, P = 0.049) appeared to exhibit a potential protective effect against frailty.

The findings of this study provide further evidence for the genetic correlation between gut microbiota and accelerated aging as well as frailty, enhancing the understanding of the role of gut microbiota in aging-related processes. However, the underlying mechanisms and potential clinical applications require further investigation before any targeted interventions can be developed.

High fiber (34-36 g/day) diets are recommended during pregnancy due to inverse associations with constipation and adverse pregnancy health outcomes, including pre-eclampsia and gestational diabetes. However, the mechanism for this protective effect is poorly defined. Fiber may be protective due to its impact on the composition and function of specific bacteria within the pregnancy gut microbiome. The purpose of this analysis was to investigate whether a sub-sample of cohort study participants in their third trimester met daily dietary fiber and vegetable intake recommendations and, in turn, how this impacted bacterial composition and butyrate-producing genes within the gut microbiome.

Pregnant participants (n = 52) provided stool samples and survey data, which were used to calculate fiber and vegetable intake. Genomic DNA was extracted from the stool samples, followed by PCR to amplify the V4 region of the 16S rRNA gene. Amplicons were sequenced and mapped to the RDP reference. Quantitative real-time PCR was used to measure the abundance of bacterial genes for butyrate production.

Of the pregnant participants in this sample, 84.7% and 92.3% failed to meet recommendations in the Dietary Guidelines for Americans for dietary fiber and vegetable intake, respectively. All four participants who met the vegetable recommendation were a subset of those who met the fiber recommendation. The participants who met the pregnancy fiber recommendation had gut microbiotas with greater alpha diversity (Shannon and Inverse Simpson) than those who did not. However, there was no association between dietary fiber intake and the abundance of bacterial genes for butyrate production.

This research suggests that general fiber intake during pregnancy has a modest association with the gut bacterial community. These preliminary results demonstrate a need to improve fiber intake during pregnancy. Further, studies that measure the relationship between dietary intake of specific types of fiber and associations with specific gut bacterial community members and their functions are needed.

Human milk-derived probiotics are beneficial bacteria that provide gestational health benefits, for both pregnant women and their offspring. The study aims to investigate whether the administration of human milk-derived probiotic L. plantarum HM-P2 could effectively influence gestational health.

The gestational humanized microbiome model was built by fecal microbiome transplant from gestational women into germ-free (GF) mice.

HM-P2 was successfully planted and increased the top crypt depth of the colon, and microbes such as L. reuteri, Anaerofilum sp. An201, and Gemmiger were up-regulated in the HM-P2 group throughout gestation. HM-P2 significantly promoted the contents of intestinal caproic acid, bile acids, and tryptophan catabolites such as serotonin. Gut microbes were associated with these bile acids and tryptophans.

HM-P2 could modulate the microbial community and microbial metabolites in gestational humanized GF mice. This probiotic strain could be a potential gestational dietary supplement with health benefits.

Pervasive environmental pollutants, specifically particulate matter (PM2.5), possess the potential to disrupt homeostasis of female thyroid hormone (TH). However, the precise mechanism underlying this effect remains unclear. In this study, we established a model of PM2.5-induced thyroid damage in female rats through intratracheal instillation and employed histopathological and molecular biological methods to observe the toxic effects of PM2.5 on the thyroid gland. Transcriptome gene analysis and 16S rRNA sequencing were utilized to investigate the impact of PM2.5 exposure on the female rat thyroid gland. Furthermore, based on the PM2.5-induced toxic model in female rats, we evaluated its effects on intestinal microbiota, TH levels, and indicators of thyroid function. The findings revealed that PM2.5 exposure induced histopathological damage to thyroid tissue by disrupting thyroid hormone levels (total T3 [TT3], (P < 0.05); total T4 [TT4], (P < 0.05); and thyrotropin hormone [TSH], (P < 0.05)) and functional indices (urine iodine [UI], P > 0.05), thus further inducing histopathological injuries. Transcriptome analysis identified differentially expressed genes (DEGs), primarily concentrated in interleukin 17 (IL-17), forkhead box O (FOXO), and other signaling pathways. Furthermore, exposure to PM2.5 altered the composition and abundance of intestinal microbes. Transcriptome and microbiome analyses demonstrated a correlation between the DEGs within these pathways and the flora present in the intestines. Moreover, 16 S rRNA gene sequencing analysis or DEGs combined with thyroid function analysis revealed that exposure to PM2.5 significantly induced thyroid hormone imbalance. We further identified key DEGs involved in thyroid function-relevant pathways, which were validated using molecular biology methods for clinical applications. In conclusion, the homeostasis of the "gut-thyroid" axis may serve as the underlying mechanism for PM2.5-induced thyrotoxicity in female rats.

Background: A high-fat diet (HFD) is generally associated with an increased risk of mental disorders that constitute a sizeable worldwide health. A HFD results in the gut microbiota-brain axis being altered and linked to mental disorders. Hypocretin-1, which can promote appetite, has been previously confirmed to be associated with depression. However, no exact relationship has been found for hypocretin between depression and HFDs. Methods: Adult male SD rats were randomly assigned to either a HFD or a normal diet for eight weeks, followed by behavioral tests and plasma biochemical analyses. Then, we investigated the protein and mRNA levels of inflammation-related factors in the hippocampus. We also observed morphological changes in brain microglia and lipid accumulation. Additionally, metagenomic and metabolomic analyses of gut microbiomes were performed. 3T3-L1 cells were utilized in vitro to investigate the impact of hypocretin receptor 1 antagonists (SB334867) on lipid accumulation. To consider the connection between the brain and adipose tissue, we used a conditioned medium (CM) treated with 3T3-L1 cells to observe the activation and phagocytosis of BV2 cells. Following a 12-week period of feeding a HFD to C57BL/6 mice, a three-week intervention period was initiated during which the administration of SB334867 was observed. This was followed by a series of assessments, including monitoring of body weight changes and emotional problems, as well as attention to plasma biochemical levels and microglial cell phenotypes in the brain. Results: The HFD rats displayed anxiety and depressive-like behaviors. HFD rats exhibited increased plasma HDL, LDL, and TC levels. A HFD also causes an increase in hypocretin-1 and hypocretin-2 in the hypothalamus. Metagenomics and metabolomics revealed that the HFD caused an increase in the relative abundance of associated inflammatory bacteria and decreased the abundance of anti-inflammatory and bile acid metabolites. Compared with the CTR group, hippocampal microglia in the HFD group were significantly activated and accompanied by lipid deposition. At the same time, protein and mRNA expression levels of inflammation-related factors were increased. We found that SB334867 could significantly reduce lipid accumulation in 3T3-L1 cells after differentiation. The expression of inflammatory factors decreased in the SB334867 group. The administration of SB334867 was found to reverse the adverse effects of the HFD on body weight, depressive-like behaviour and anxiety-like mood. Furthermore, this treatment was associated with improvements in plasma biochemical levels and a reduction in the number of microglia in the brain. Conclusions: In summary, our results demonstrated that a HFD induced anxiety and depressive-like behaviors, which may be linked to the increased hypocretin-1 level and lipid accumulation. Supplementation with SB334867 improved the above. These observations highlight the possibility of hypocretin-1 inducing the risk of HFD-associated emotional dysfunctions.

The polysaccharides from Auricularia auricula (AAPs), containing a large number of O-acetyl groups that are related to the physiological and biological properties, seem to be potential prebiotics like other edible fungus polysaccharides. In the present study, therefore, the alleviating effects of AAPs and deacetylated AAPs (DAAPs, prepared from AAPs by alkaline treatment) on nonalcoholic fatty liver disease (NAFLD) induced by high-fat and high-cholesterol diet combined with carbon tetrachloride were investigated. The results revealed that both AAPs and DAAPs could effectively relieve liver injury, inflammation and fibrosis, and maintain intestinal barrier function. Both AAPs and DAAPs could modulate the disorder of gut microbiota and altered the composition of gut microbiota with enrichment of Odoribacter, Lactobacillus, Dorea and Bifidobacterium. Further, the alteration of gut microbiota, especially enhancement of Lactobacillus and Bifidobacterium, was contributed to the changes of bile acids (BAs) profile with increased deoxycholic acid (DCA). Farnesoid X receptor could be activated by DCA and other unconjugated BAs, which participated the BAs metabolism and alleviated the cholestasis, then protected against hepatitis in NAFLD mice. Interestingly, it was found that the deacetylation of AAPs negatively affected the anti-inflammation, thereby reducing the health benefits of A. auricula-derived polysaccharides.

Aim: Clostridia are relevant commensals of the human gut due to their major presence and correlations to the host. In this study, we investigated intestinal Clostridia of 51 healthy subjects and reconstructed their taxonomy and phylogeny. The relatively small number of intestinal Clostridia allowed a systematic whole genome approach based on average amino acid identity (AAI) and core genome with the aim of revising the current classification into genera and determining evolutionary relationships. Methods: 51 healthy subjects' metagenomes were retrieved from public databases. After the dataset's validation through comparison with Human Microbiome Project (HMP) samples, the metagenomes were profiled using MetaPhlAn3 to identify the population ascribed to the class Clostridia. Intestinal Clostridia genomes were retrieved and subjected to AAI analysis and core genome identification. Phylogeny investigation was conducted with RAxML and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithms, and SplitsTree for split decomposition. Results: 225 out of 406 bacterial taxonomic units were ascribed to Bacillota [Firmicutes], among which 124 were assigned to the class Clostridia. 77 out of the 124 taxonomic units were referred to a species, altogether covering 87.7% of Clostridia abundance. According to the lowest AAI genus boundary set at 55%, 15 putative genera encompassing more than one species (G1 to G15) were identified, while 19 species did not cluster with any other one and each appeared to belong to a diverse genus. Phylogenetic investigations highlighted that most of the species clustered into three main evolutive clades. Conclusion: This study shed light on the species of Clostridia colonizing the gut of healthy adults and pinpointed several gaps in knowledge regarding the taxonomy and the phylogeny of Clostridia.

Acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation poses one of the most vexing challenges. Gut microbiota dysbiosis can proceed aGVHD and mesenchymal stem cells (MSCs) have promising therapeutic potential for aGVHD. However, whether hAMSCs affect the gut microbiota during aGVHD mitigation remains unknown. Accordingly, we sought to define the effects and underlying mechanisms of human amniotic membrane-derived MSCs (hAMSCs) regulating the gut microbiota and intestinal immunity in aGVHD. By establishing humanized aGVHD mouse models and hAMSCs treatment, we found that hAMSCs significantly ameliorated aGVHD symptoms, reversed the immune imbalance of T cell subsets and cytokines, and restored intestinal barrier. Moreover, the diversity and composition of gut microbiota were improved upon treatment with hAMSCs. Spearman's correlation analysis showed that there was a correlation between the gut microbiota and tight junction proteins, immune cells as well as cytokines. Our research suggested that hAMSCs alleviated aGVHD by promoting gut microbiota normalization and regulating the interactions between the gut microbiota and intestinal barrier, immunity.

Recent pandemic infection caused by SARS-CoV-2 (COVID-19) led the scientific community to investigate the possible causes contributing to the physiopathology of this disease. In this context, analyses of the intestinal microbiota highlighted possible correlation between host-associated bacterial communities and development of the COVID-19. Nevertheless, a detailed investigation of the role of the human microbiota in the severity of the symptoms of this disease is still lacking. This study performed a comprehensive meta-analysis of 323 faecal samples from public and novel Italian data sets based on the shotgun metagenomic approach. In detail, the comparative analyses revealed possible differences in the microbial biodiversity related to the individual health status, highlighting a species richness decrease in COVID-19 patients with a severe prognosis. Moreover, healthy subjects resulted characterized by a higher abundance of protective and health-supporting bacterial species, while patients affected by COVID-19 disease displayed a significant increase of opportunistic pathogen bacteria involved in developing putrefactive dysbiosis. Furthermore, prediction of the microbiome functional capabilities suggested that individuals affected by COVID-19 subsist in an unbalanced metabolism characterized by an overrepresentation of enzymes involved in the protein metabolism at the expense of carbohydrates oriented pathways, which can impact on disease severity and in excessive systemic inflammation.