Shifts In Gut Microbiota Composition Research Articles

High-Fat Diet Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites

Dietary fat intake is associated with increased risk of colorectal cancer (CRC). We examined the role of high-fat diet (HFD) in driving CRC through modulating gut microbiota and metabolites. HFD or control diet was fed to mice littermates in CRC mouse models of an azoxymethane (AOM) model and Apcmin/+ model, with or without antibiotics cocktail treatment. Germ-free mice for fecal microbiota transplantation were used for validation. Gut microbiota and metabolites were detected using metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Gut barrier function was determined using lipopolysaccharides level and transmission electron microscopy. HFD promoted colorectal tumorigenesis in both AOM-treated mice and Apcmin/+ mice compared with control diet-fed mice. Gut microbiota depletion using antibiotics attenuated colon tumor formation in HFD-fed mice. A significant shift of gut microbiota composition with increased pathogenic bacteria Alistipessp.Marseille-P5997 and Alistipessp.5CPEGH6, and depleted probiotic Parabacteroides distasonis, along with impaired gut barrier function was exhibited in HFD-fed mice. Moreover, HFD-modulated gut microbiota promotes colorectal tumorigenesis in AOM-treated germ-free mice, indicating gut microbiota was essential in HFD-associated colorectal tumorigenesis. Gut metabolites alteration, including elevated lysophosphatidic acid, which was confirmed to promote CRC cell proliferation and impair cell junction, was also observed in HFD-fed mice. Moreover, transfer of stools from HFD-fed mice to germ-free mice without interference increased colonic cell proliferation, impaired gut barrier function, and induced oncogenic genes expression. HFD drives colorectal tumorigenesis through inducing gut microbial dysbiosis, metabolomic dysregulation with elevated lysophosphatidic acid, and gut barrier dysfunction in mice.

ZiBuPiYin Recipe Prevented and Treated Cognitive Decline in ZDF Rats With Diabetes-Associated Cognitive Decline via Microbiota-Gut-Brain Axis Dialogue.

Gut microbiota is becoming one of the key determinants in human health and disease. Shifts in gut microbiota composition affect cognitive function and provide new insights for the prevention and treatment of neurological diseases. Diabetes-associated cognitive decline (DACD) is one of the central nervous system complications of type 2 diabetes mellitus (T2DM). ZiBuPiYin recipe (ZBPYR), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of T2DM and prevention of DACD. However, the contribution of ZBPYR treatment to the interaction between the gut microbiota and metabolism for preventing and treating DACD remains to be clarified. Here, we investigate whether the gut microbiota plays a key role in ZBPYR-mediated prevention of DACD and treatment of T2DM via incorporating microbiomics and metabolomics, and investigate the links between the microbiota–gut–brain axis interaction and the efficacy of ZBPYR in ZDF rats. In the current study, we found that ZBPYR treatment produced lasting changes in gut microbiota community and metabolites and remotely affected hippocampus metabolic changes, thereby improving memory deficits and reversing β-amyloid deposition and insulin resistance in the brain of ZDF rats from T2DM to DACD. This may be related to a series of metabolic changes affected by gut microbiota, including alanine, aspartic acid, and glutamic acid metabolism; branched-chain amino acid metabolism; short-chain fatty acid metabolism; and linoleic acid/unsaturated fatty acid metabolism. In summary, this study demonstrates that prevention and treatment of DACD by ZBPYR partly depends on the gut microbiota, and the regulatory effects of bacteria-derived metabolites and microbiota–gut–brain axis are important protective mechanisms of ZBPYR.

The Effect of Probiotics on Health Outcomes in the Elderly: A Systematic Review of Randomized, Placebo-Controlled Studies.

Increasing evidence suggests that probiotic supplementation may be efficacious in counteracting age-related shifts in gut microbiota composition and diversity, thereby impacting health outcomes and promoting healthy aging. However, randomized controlled trials (RCTs) with probiotics in healthy older adults have utilized a wide variety of strains and focused on several different outcomes with conflicting results. Therefore, a systematic review was conducted to determine which outcomes have been investigated in randomized controlled trials with probiotic supplementation in healthy older adults and what has been the effect of these interventions. For inclusion, studies reporting on randomized controlled trials with probiotic and synbiotic supplements in healthy older adults (defined as minimum age of 60 years) were considered. Studies reporting clinical trials in specific patient groups or unhealthy participants were excluded. In addition to assessment of eligibility and data extraction, each study was examined for risk of bias and quality assessment was performed by two independent reviewers. Due to the heterogeneity of outcomes, strains, study design, duration, and methodology, we did not perform any meta-analyses and instead provided a narrative overview of the outcomes examined. Of 1997 potentially eligible publications, 17 studies were included in this review. The risk of bias was low, although several studies failed to adequately describe random sequence generation, allocation concealment, and blinding. The overall study quality was high; however, many studies did not include sample calculations, and the majority of studies had a small sample size. The main outcomes examined in the trials included microbiota composition, immune-related measurements, digestive health, general well-being, cognitive function, and lipid and other biomarkers. The most commonly assessed outcome with the most consistent effect was microbiota composition; all but one study with this outcome showed significant effects on gut microbiota composition in healthy older adults. Overall, probiotic supplementation had modest effects on markers of humoral immunity, immune cell population levels and activity, as well as the incidence and duration of the common cold and other infections with some conflicting results. Digestive health, general-well-being, cognitive function, and lipid and other biomarkers were investigated in a very small number of studies; therefore, the impact on these outcomes remains inconclusive. Probiotics appear to be efficacious in modifying gut microbiota composition in healthy older adults and have moderate effects on immune function. However, the effect of probiotic supplementation on other health outcomes remains inconclusive, highlighting the need for more well-designed, sufficiently-powered studies to investigate if and the mechanisms by which probiotics impact healthy aging.

No interplay between gut microbiota composition and the lipopolysaccharide-induced innate immune response in humans in vivo.

ObjectiveAnimal studies have demonstrated the extensive interplay between the gut microbiota and immunity. Moreover, in critically ill patients, who almost invariably suffer from a pronounced immune response, a shift in gut microbiota composition is associated with infectious complications and mortality. We examined the relationship between interindividual differences in gut microbiota composition and variation in the in vivo cytokine response induced by bacterial lipopolysaccharide (LPS). Furthermore, we evaluated whether an LPS challenge alters the composition of the gut microbiota.MethodsHealthy male volunteers received an intravenous bolus of 2 ng kg−1 LPS (n = 70) or placebo (n = 8). Serial plasma concentrations of tumor necrosis factor‐α, interleukin (IL)‐6, IL‐8 and IL‐10 were measured, and subjects were divided into high and low cytokine responders. Gut microbiota composition was determined using 16s RNA gene sequencing of faecal samples obtained 1 day before (baseline) and 1 day and 7 days following the LPS challenge.ResultsBaseline microbiota composition, analysed by principal coordinate analysis and random forest analysis, did not differ between high and low responders for any of the four measured cytokines. Furthermore, baseline microbiota diversity (Shannon and Chao indices) was similar in high and low responders. No changes in microbiota composition or diversity were observed at 1 and 7 days following the LPS challenge.ConclusionOur results indicate that existing variation in gut microbiota composition does not explain the observed variability in the LPS‐induced innate immune response. These findings strongly argue against the interplay between the gut microbiota composition and the innate immune response in humans.

Gut Microbiota Shift in Obese Adolescents Born by Cesarean Section

Background: It is known that in the early postnatal period a variety of factors affect the gut microbiota (GM) composition, including delivery mode. The effect of delivery mode on the human GM in the late postnatal period remains unexplored. A shift of GM composition due to delivery mode may contribute to the development of obesity in adulthood. Methods and Results: The study included six adolescents aged between 11 and 17 years treated and examined at the Clinic of the Scientific Center for Family Health and Human Reproduction (Irkutsk, Russia) in 2016. Stool samples were collected following the standard operating procedures according to the International Human Microbiome Standards. Metasequencing of V3-V4 variable regions of the 16S rRNA gene was performed by the Novogene Company (China) on the Illumina platform. Bioinformatic analysis was done by the bri-shur.com services. Sequencing reads were presented as normalized values. In general, the GM composition of obese adolescents born by cesarean section was characterized by composition heterogeneity within the Bacteroidetes phylum and the dominance of certain phylotypes as signs of dysbiosis for each adolescent. We detected an increased abundance of phyla Bacteroides and Proteobacteria, and an absence of Tenericutes in obese adolescents born by Caesarean section. On the level of genera, the prevalence of Bacteroides and Bacteroides S24-7 phylotypes, and the absence of the RF39 phylotype, led to the GM shift associated with a cesarean section or obesity. Conclusion: Obese adolescents born by cesarean section delivery present the shift in GM composition.

Metagenomics in bioflocs and their effects on gut microbiome and immune responses in Pacific white shrimp

Biofloc systems generate and accumulate microbial aggregates known as bioflocs. The presence of bioflocs has been shown to change gut bacterial diversity and stimulate innate immunity in shrimp. The microbial niche of bioflocs may therefore have the potential to drive shifts in the shrimp gut microbiota associated with stimulation of innate immunity. We performed shotgun metagenomic analysis and 16S rRNA-based amplicon sequencing to characterize complex bacterial members in bioflocs and the shrimp digestive tract, respectively. Moreover, we determined whether biofloc-grown shrimp with discrete gut microbiomes had an elevation in local immune-related gene expression and systemic immune activities. Our findings demonstrated that the bacterial community in bioflocs changed dynamically during Pacific white shrimp cultivation. Metagenomic analysis revealed that Vibrio comprised 90% of the biofloc population, while Pseualteromonas, Photobacterium, Shewanella, Alteromonas, Bacillus, Lactobacillus, Acinetobacter, Clostridium, Marinifilum, and Pseudomonas were also detected. In the digestive tract, biofloc-grown shrimp maintained the presence of commensal bacteria including Vibrio, Photobacterium, Shewanella, Granulosicoccus, and Ruegeria similar to control shrimp. However, Vibrio and Photobacterium were significantly enriched and declined, respectively, in biofloc-grown shrimp. The presence of bioflocs upregulated immune-related genes encoding serine proteinase and prophenoloxidase in digestive organs which are routinely exposed to gut microbiota. Biofloc-grown shrimp also demonstrated a significant increase in systemic immune status. As a result, the survival rate of biofloc-grown shrimp was substantially higher than that of the control shrimp. Our findings suggested that the high relative abundance of vibrios in bioflocs enriched the number of vibrios in the digestive tract of biofloc-grown shrimp. This shift in gut microbiota composition may be partially responsible for local upregulation of immune-related gene expression in digestive organs and systemic promotion of immune status in circulating hemolymph.

Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation.

Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.

Gestational Diabetes Mellitus Is Associated with Reduced Dynamics of Gut Microbiota during the First Half of Pregnancy

Women with gestational diabetes mellitus (GDM) have different gut microbiota in late pregnancy compared to women without GDM. It remains unclear whether alterations of gut microbiota can be identified prior to the diagnosis of GDM. This study characterized dynamic changes of gut microbiota from the first trimester (T1) to the second trimester (T2) and evaluated their relationship with later development of GDM. Compared with the control group (n = 103), the GDM group (n = 31) exhibited distinct dynamics of gut microbiota, evidenced by taxonomic, functional, and structural shifts from T1 to T2. Linear discriminant analysis (LDA) revealed that there were 10 taxa in T1 and 7 in T2 that differed in relative abundance between the GDM and control groups, including a consistent decrease in the levels of Coprococcus and Streptococcus in the GDM group. While the normoglycemic women exhibited substantial variations of gut microbiota from T1 to T2, their GDM-developing counterparts exhibited clearly reduced inter-time point shifts, as corroborated by the results of Wilcoxon signed-rank test and balance tree analysis. Moreover, cooccurrence network analysis revealed that the interbacterial interactions in the GDM group were minimal compared with those in the control group. In conclusion, lower numbers of dynamic changes in gut microbiota in the first half of pregnancy are associated with the development of GDM.IMPORTANCE GDM is one of the most common metabolic disorders during pregnancy and is associated with adverse short-term and long-term maternal and fetal outcomes. The aim of this study was to examine the connection between dynamic variations in gut microbiota and development of GDM. Whereas shifts in gut microbiota composition and function have been previously reported to be associated with GDM, very little is known regarding the early microbial changes that occur before the diagnosis of GDM. This study demonstrated that the dynamics in gut microbiota during the first half of pregnancy differed significantly between GDM and normoglycemic women. Our findings suggested that gut microbiota may potentially serve as an early biomarker for GDM.

Faecal virome transplantation decreases symptoms of type 2 diabetes and obesity in a murine model

ObjectiveDevelopment of obesity and type 2 diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria...

The Gut-liver Axis in Immune Remodeling: New insight into Liver Diseases.

The gut microbiota consists of a dynamic multispecies community of bacteria, fungi, archaea, and protozoans, playing a fundamental role in the induction, training, and function of the host immune system. The liver is anatomically and physiologically linked to the gut microbiota via enterohepatic circulation, specifically receiving intestine-derived blood through the portal vein. The gut microbiota is crucial for maintaining immune homeostasis of the gut-liver axis. A shift in gut microbiota composition can result in activation of the mucosal immune response causing homeostasis imbalance. This imbalance results in translocation of bacteria and migration of immune cells to the liver, which is related to inflammation-mediated liver injury and tumor progression. In this review, we outline the role of the gut microbiota in modulating host immunity and summarize novel findings and recent advances in immune-based therapeutics associated with the gut-liver axis. Moving forward, a deep understanding of the microbiome-immune-liver axis will provide insight into the basic mechanisms of gut microbiota dysbiosis affecting liver diseases.

Potential correlation between carbohydrate-active enzyme family 48 expressed by gut microbiota and the expression of intestinal epithelial AMP-activated protein kinase β.

The expression of the carbohydrate-active enzyme family and related genes is known to be influenced by the response of intestinal microbiota to dietary changes. However, it is uncertain whether this is caused by variation in the intestinal microecology. In this study, metabolite analysis, 16S rDNA sequencing, metagenomics, and Western blotting were employed to investigate the effects of dietary intervention on the composition of gut microbiota and microbiota-mediated changes. The results showed that compared with the low fiber-fed group, the fiber diet-fed mice displayed a shift in gut microbiota composition to contain more members of phylum Bacteroidetes, accompanied by higher proportions of Akkermansia and typical probiotic Bifidobacterium. Moreover, correlations were found between microbial genes coding for carbohydrate-binding module family 48 (CBM48) and intestinal epithelial expression levels of AMPK β. This finding provides new insight for elucidating the contribution of dietary intervention through AMPK regulation linked to the microbial carbohydrate-binding family. PRACTICAL APPLICATIONS: The relationship suggested by these data will provide theoretical and applied foundations for the development of potential intervention targeting the interaction between gut microbiota and host health, particularly the use of dietary fiber as a medically relevant food. Additionally, a better understanding of the interactions between gut microbiota and intestinal epithelial will inform the development of gut microbiota intervention as a health-promoting procedure.

Insights into the Potential of the Atlantic Cod Gut Microbiome as Biomarker of Oil Contamination in the Marine Environment.

Background: Microorganisms are widespread in all environments, including in and on animal bodies. The gut microbiome has an essential influence on fish health, and is affected by several persistent and harmful organic and inorganic contaminants. Considering the shifts in gut microbiota composition observed in those studies, we hypothesized that certain microbial groups in the gut can serve as indicators of pollution. To test this hypothesis, we explored the possibility of identifying key microbial players that indicate environmental contamination. Methods: Published 16S rRNA gene amplicon sequencing data generated from the gut microbiota of Atlantic cod caught in geographically different Norwegian waters were used for bacterial diversity comparison. Results: Different microbiomes were identified between the northern Norway and southern Norway samples. Several bacterial genera previously identified as polycyclic aromatic hydrocarbon degraders were present only in the samples collected in the southern Norway area, suggesting fish contamination with oil-related compounds. Conclusions: The results contribute to the identification of bacterial taxa present in the Atlantic cod gut that indicate fish exposure to contaminants in the marine environment.

Stages of pregnancy and weaning influence the gut microbiota diversity and function in sows.

AimsThe gut microbiota is believed to play important roles in the health of pregnant mammals, including their nutrient metabolism, immune programming and metabolic regulation. However, until recently, the shifts in gut microbiota composition and faecal and blood metabolic activity during different stages of pregnancy had not been investigated.Methods and ResultsWe investigated the shifts in backfat thickness, plasma and faecal metabolites and gut microbiota on days 30, 60, 90 and 110 of pregnancy and on day 21 after parturition (weaning) in sows. The backfat thickness of sows did not significantly differ among the different stages of pregnancy. The plasma concentrations of lipid metabolites, including triacylglycerol (TG), total cholesterol, high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol and calcium were reduced (P < 0·05) during pregnancy. In addition, the concentration of these metabolites, except TG, reached their maximum at the time of weaning. We also found that Tenericutes, Fibrobacteres and Cyanobacteria varied significantly according to the stages of pregnancy in sows (P < 0·05). Most of the genera, such as Clostridiales, Desulfovibrio, Mogibacteriaceae and Prevotella, increased (P < 0·05) with the progression of pregnancy and decreased (P < 0·05) at weaning. The alpha diversity values (i.e., Shannon diversity and observed species) of sow gut microbiota increased (P < 0·05) from pregnancy to weaning. Pregnancy stages also significantly influenced (P < 0·05) the community structure (beta diversity) of gut microbiota. The progression of pregnancy was associated with changes in lipid metabolism and several carbohydrate‐degradation bacteria (i.e., Prevotella, Succinivibrio, Bacteroides and Parabacteroides).ConclusionsAlthough causal links between the measured parameters remain hypothetical, these findings suggest that the increased diversity and concentration of beneficial gut microbes are associated with the metabolism of pregnant sows.Significance and Impact of the StudyManipulation of the sow gut microbiota composition may potentially influence metabolism and health during pregnancy.

Bacillus licheniformis Zhengchangsheng® attenuates DSS-induced colitis and modulates the gut microbiota in mice.

Human inflammatory bowel disease (IBD) and experimental colitis models in mice are associated with shifts in gut microbiota composition, and several probiotics are widely used to improve gastrointestinal health. Here, we investigated whether the probiotic Bacillus licheniformis Zhengchangsheng® (BL) ameliorates dextran sulphate sodium (DSS)-induced colitis through alteration of the gut microbiota. Experimental colitis was induced in BALB/C mice by dissolving 3% DSS in their drinking water for 7 days, which were gavaged with 0.2 ml phosphate-buffered saline or BL (3×107 cfu/ml) once a day. Administration of BL attenuated several effects of DSS-induced colitis, including weight loss, increased disease activity index, and disrupted intestinal barrier integrity. In addition, BL mitigated the reduction in faecal microbiota richness in DSS treated mice. Interestingly, BL was found to reduce the elevated circulating endotoxin level in mice with colitis by modulating the microbial composition of the microbiota, and this was highly associated with a proportional decrease in gut Bacteroidetes. Our results demonstrate that BL can attenuate DSS-induced colitis and provide valuable insight into microbiota interactions during IBD.

Sa1922 – Distinct Shifts in Gut Microbiota Composition Throughout the Gastrointestinal Tract During Healthy Aging

Sa1922 – Distinct Shifts in Gut Microbiota Composition Throughout the Gastrointestinal Tract During Healthy Aging

HIV and the Gut Microbiota: Composition, Consequences, and Avenues for Amelioration.

We discuss recent advances in understanding of gut bacterial microbiota composition in HIV-infected subjects and comment on controversies. We discuss the putative effects of microbiota shifts on systemic inflammation and HIV disease progression and potential mechanisms, as well as ongoing strategies being developed to modulate the gut microbiota in humans for amelioration of infectious and inflammatory diseases. Lifestyle and behavioral factors relevant to HIV infection studies have independent effects on the microbiota. Microbial metabolism of immunomodulatory compounds and direct immune stimulation by translocation of microbes are putative mechanisms contributing to HIV disease. Fecal microbiota transplantation, microbial enzyme inhibition, phage therapy, and rationally selected probiotic cocktails have emerged as promising strategies for microbiota modulation. Numerous surveys of the HIV gut microbiota matched for lifestyle factors suggest consistent shifts in gut microbiota composition among HIV-infected subjects. Evidence exists for a complex pathogenic role of the gut microbiota in HIV disease progression, warranting further study.

NAG‐1/GDF15 inhibits HFD‐induced obesity and inflammation by modulating gut microbiota

Nonsteroidal anti‐inflammatory drug‐activated gene (NAG‐1) or growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor beta (TGF‐β) superfamily. Mice expressing NAG‐1/GDF15 have been shown to be resistant to high fat diet (HFD)‐induced obesity and inflammation. However, the exact mechanism underlying the anti‐obesity effects of NAG‐1/GDF15 remains unknown. The objective of this study was to examine whether the anti‐obesity effects of NAG‐1/GDF15 is associated with gut microbiota modulation and gut barrier function regulation. First, we confirmed that NAG‐1/GDF15 Tg mice are resistant to dietary induced obesity and inflammation. These mice also demonstrated improved insulin sensitivity compared to Wt littermates. We then found these phenotypic differences were correlated with differences in the composition of gut microbiota, gut barrier function and short chain fatty acids compositions in feces as determined by standard molecular biological methods. In addition, HFD reduced the expression of Cyp7a1, Cyp7b1, Cyp27a1, Ntcp, Mdr2, and Oatp that regulate bile acid metabolism in liver. However, the expression of these genes were increased in NAG‐1/GDF15 Tg mice. Furthermore, antibacterial peptide (Reg3g, Lyz‐1 and Defa) and MUC2 in small intestine were up‐regulated in NAG‐1/GDF15 Tg mice. We also found that NGA‐1/GDF15 down‐regulate the expression of TLR4 and its downstream signals in fat, liver and small intestines at both mRNA and protein levels as determined by Western blot and qRT‐PCR. Finally, we transplanted feces from NAG‐1/GDF15 mice into pseudo germ‐free mice and fed the mice with HFD and found that a shift in gut microbiota composition from NAG‐1/GDF15 mice could inhibit the development of obesity and inflammation. Taken together, our results indicate that the protection role of NAG‐1/GDF15 against HFD‐induced obesity and inflammation is mediated, at least in part, by the modulation of gut microbiota, function of gut barrier, and bile acid metabolism.Support or Funding InformationNational Natural Science Foundation of China Grant No. 81400822.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites.

Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3days followed by 4days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection. Furthermore, FMD decreased the number of glial cells as well as the release of TNF-α and IL-1β in PD mice, showing that FMD also inhibited neuro-inflammation. 16S and 18S rRNA sequencing of fecal microbiota showed that FMD treatment modulated the shifts in gut microbiota composition, including higher abundance of Firmicutes, Tenericutes, and Opisthokonta and lower abundance of Proteobacteria at the phylum level in PD mice. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed that FMD modulated the MPTP-induced lower propionic acid and isobutyric acid, and higher butyric acid and valeric acid and other metabolites. Transplantation of fecal microbiota, from normal mice with FMD treatment to antibiotic-pretreated PD mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD. These findings demonstrate that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.

The profiles of dysbiotic microbial communities.

Alterations in the human gut microbiota play an important role in disease pathogenesis. Although next-generation sequencing has provided observational evidence linking shifts in gut microbiota composition to alterations in the human host, underlying mechanisms remain elusive. Metabolites generated within complex microbial communities and at the crossroads with host cells may be able to explain the impact of the gut microbiome on human homeostasis. Emerging technologies including novel culturing protocols, microfluidic systems, engineered organoids, and single-cell imaging approaches are providing new perspectives from which the gut microbiome can be studied paving the way to new diagnostic markers and personalized therapeutic interventions.

Modulation of fat metabolism and gut microbiota by resveratrol on high-fat diet-induced obese mice.

PurposeThe antioxidant resveratrol (RSV) has low bioavailability and can reach the colon to access the gut microbial ecosystem. RSV administration together with high-fat diet prevented abnormal changes of intestinal microbiota. However, whether or not RSV can reshape the intestinal microbiota of obese mice and alleviate obesity-related diseases remains to be studied. This study aimed to explore the role of RSV in alleviating high-fat-induced obesity and its relationship with oxidative stress and gut microbiota.MethodsMale C57BL/6 mice were divided into five groups and administered for 16 weeks with: standard diet (CON), high-fat diet (60% energy for lard, HFD), and HFD with low, medium, and high dose of RSV, 50, 75, and 100 mg/kg body weight administered daily via drinking water, respectively.ResultsMedium and high RSV treatment significantly prevented body weight gain, decreased relative weight of liver and adipose tissue compared with HFD (P<0.05). All doses significantly prevented HFD-induced increase of serum triglyceride, low density lipoprotein cholesterol, glucose, and endotoxemia (P<0.05). Medium and high dose also prevented chronic inflammation by decreasing serum interleukin-1 and tumor necrosis factor-alpha (P<0.05), and oxidative stress in liver and brain indicated by increase in superoxide dismutase, catalase, glutathione peroxidase activity (P<0.05). Formation of malondialdehyde was prevented by all doses compared with HFD (P<0.05). Both medium and high doses of RES increased alpha diversity of gut microbiota according to the Chao1 and Shannon indices (P<0.05). Medium dose induced obvious shift in gut microbiota composition according to principal component analysis. High dose of RSV effectively prevented HFD-induced increase of Coriobacteriaceae and Desulfovi-brionaceae (P<0.05), which show a significant correlation with body weight (r>0.8 P<0.00).ConclusionRSV prevented HFD-induced endotoxemia, oxidative stress, and gut microbiota change.