The gut microbiota is crucial in the pathogenesis of obesity. Abdominal obesity is known to significantly increase the risk of metabolic syndrome and cardiovascular disease, so further study is needed to investigate the changes of intestinal microorganisms in patients with excessive visceral fat. In our study, 41 people (n = 41) with normal body mass index (BMI) (18.5 ≤ BMI < 23.9) were included and divided into the low visceral fat area (L-VFA) group (n = 23, VFA < 100 cm²) and the high visceral fat area (H-VFA) group (n = 18, VFA ≥ 100 cm²). Several clinical indicators of the H-VFA group were significantly higher than those of the L-VFA group, including the waist circumference (WC), the fasting blood glucose (FBG), the triglyceride (TG), the total cholesterol (TC), the low-density lipoprotein cholesterol (LDL), the serum uric acid (SUA), the white blood cell count (WBC), the blood neutrophil count (NEC), and the blood lymphocyte count (LYC). Using whole-genome shotgun sequencing, we found that the types of the intestinal microbiota of H-VFA patients were different from those of the L-VFA patients, with 18 bacteria enriched in the H-VFA group and nine bacteria in the L-VFA group. A total of 16 species of gut microbes showed a strong correlation with VFA, and Escherichia coli has the strongest correlation, followed by Mitsuokella unclassified, Bifidobacterium longum, Escherichia unclassified, Ruminococcus torques, Dialister succinatiphilus, Eubacterium hallii, and Ruminococcus gnavus. Compared to the VFA, only two species show a strong correlation with BMI and WC. Further functional genetic studies suggested that the degradation of short-chain fatty acids (SCFAs) and the generation of lipopolysaccharide (LPS) might be related to visceral fat accumulation. Together, visceral fat was more closely correlated with the gut microbiome compared with BMI and WC. It suggested an intrinsic connection between the gut microbiome and visceral fat and its related metabolic disorders. Specific microbial species and pathways associated with visceral fat accumulation might contribute to new targeted therapies for visceral fat and its metabolic disorders.

Metabolic syndrome (MetS) is a wide-ranging disorder, which includes insulin resistance, altered glucose and lipid metabolism, and increased blood pressure and visceral obesity. MetS symptoms combine to result in a significant increase in cardiovascular risk. It is therefore critical to treat MetS in the early stages of the disorder. In this study, 123 MetS patients and 304 controls were recruited to determine whether the gut microbiome plays a role in MetS development and progression. By using whole-genome shotgun sequencing, we found that the gut microbiomes of MetS patients were different from those of controls, with MetS patients possessing significantly lower gut microbiome diversity. In addition, 28 bacterial species were negatively correlated with waist circumstance, with Alistipes onderdonkii showing the strongest correlation, followed by Bacteroides thetaiotaomicron, Clostridium asparagiforme, Clostridium citroniae, Clostridium scindens, and Roseburia intestinalis. These species were also enriched in controls relative to MetS patients. In addition, pathways involved in the biosynthesis of carbohydrates, fatty acids, and lipids were enriched in the MetS group, indicating that microbial functions related to fermentation may play a role in MetS. We also found that microbiome changes in MetS patients may aggravate inflammation and contribute to MetS diseases by inhibiting the production of short-chain fatty acids (SCFAs). Taken together, these results indicate the potential utility of beneficial gut microbiota as a potential therapeutic to alleviate MetS.

Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.

It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of “harmful bacteria” such as Megamonas hypermegale, Megamonas funiformis, Megamonas unclassified, Klebsiella pneumoniae, and Fusobacterium mortiferum and decreased levels of “beneficial bacteria” such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis. Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.

Carotid atherosclerosis (CAS) is a reflection of systemic atherosclerosis and the main pathological processes of cardiovascular disease (CVD), namely, carotid intima–media thickening, carotid plaque formation, and carotid stenosis. Accumulating evidence indicates that the gut microbiota plays an important role in CVD and gut–brain disorders, but the associations of the composition and metabolites of the gut microbiome with CAS have not been studied comprehensively. We performed a gut microbiome genome-wide association study in 31 patients with CAS and 51 healthy controls using whole-genome shotgun sequencing. We found that several risk factors (waist circumference, body mass index, diastolic blood pressure, systolic blood pressure, fasting blood glucose, glycated hemoglobin A1c, total cholesterol, triglyceride, and low-density lipoprotein cholesterol) and inflammatory markers (white blood cell count and absolute value of neutrophils) were significantly higher in the CAS group than in the control group. In addition, 21 species and 142 pathways were enriched in the CAS group, and 10 species and 1 pathway were enriched in the control group. Specifically, Bacteroides eggerthii, Escherichia coli, and Klebsiella pneumoniae were the most abundant species in the CAS group, whereas Parabacteroides unclassified, Prevotella copri, Bacteroides sp 3_1_19, and Haemophilus parainfluenzae were the most abundant species in the control group. Finally, we found that most gut microbes and microbial pathways that were enriched in the CAS group had significant positive correlations with clinical characteristics, whereas the microbes and pathways enriched in healthy controls had significant negative correlations with clinical characteristics excluding high-density lipoprotein cholesterol. In addition, the associations between gut microbes and some microbial pathways (short-chain fatty acid, lipopolysaccharide, and menaquinol biosynthesis) were identified. Our results indicate the existence of a cyclic pathway that elevates the circulating concentrations of trimethylamine-N-oxide in patients with CAS but reduces its concentrations in healthy controls.

Aging is now the most profound risk factor for almost all non-communicable diseases. Studies have shown that probiotics play a specific role in fighting aging. We used metagenomic sequencing to study the changes in gut microbes in different age groups and found that aging had the most significant effect on subjects’ gut microbe structure. Our study divided the subjects (n=614) into two groups by using 50 years as the age cut-off point for the grouping. Compared with the younger group, several species with altered abundance and specific functional pathways were found in the older group. At the species level, the abundance of Bacteroides fragilis, Bifidobacterium longum, Clostridium bolteae, Escherichia coli, Klebsiella pneumoniae, and Parabacteroides merdae were increased in older individuals. They were positively correlated to the pathways responsible for lipopolysaccharide (LPS) biosynthesis and the degradation of short-chain fatty acids (SCFAs). On the contrary, the levels of Barnesiella intestinihominis, Megamonas funiformis, and Subdoligranulum unclassified were decreased in the older group, which negatively correlated with the above pathways (p-value<0.05). Functional prediction revealed 92 metabolic pathways enriched in the older group significantly higher than those in the younger group (p-value<0.05), especially pathways related to LPS biosynthesis and the degradation of SCFAs. Additionally, we established a simple non-invasive model of aging, nine species (Bacteroides fragilis, Barnesiella intestinihominis, Bifidobacterium longum, Clostridium bolteae, Escherichia coli, Klebsiella pneumoniae, Megamonas funiformis, Parabacteroides merdae, and Subdoligranulum unclassified) were selected to construct the model. The area under the receiver operating curve (AUC) of the model implied that supplemented probiotics might influence aging. We discuss the features of the aging microbiota that make it more amenable to pre-and probiotic interventions. We speculate these metabolic pathways of gut microbiota can be associated with the immune status and inflammation of older adults. Health interventions that promote a diverse microbiome could influence the health of older adults.