Composition Of Gut Bacteria Research Articles

Postprandial factor VII activation does not increase plasma concentrations of prothrombin fragment 1 + 2 in patients with morbid obesity

IntroductionIncreased postprandial factor VII activation is observed after high-fat meals, but is not accompanied by thrombin formation in normal weight individuals. Obesity is associated with a higher circulating concentration of tissue factor (TF) and postprandial uptake of lipopolysaccharide (LPS), and this may increase thrombin formation after high-fat meals. We therefore compared postprandial effects of high-fat meals and low-fat meals on biomarkers of coagulation activation in patients with morbid obesity and investigated whether the response was associated with the gut bacteria composition. Materials and methodsA controlled cross-over study was conducted in obese patients (15 women, 5 men, mean BMI = 44.1 kg/m2), where high-fat meals (67 E% fat) and low-fat meals (16 E% fat) were served at 8:15 and 10:00 in a random order on two study days within one week. Blood samples were collected at 08:00 (fasting), 12:00, and 14:00 and analysed for triglycerides, activated FVII (FVIIa), TF, FVIIa-antithrombin (FVIIa-AT), prothrombin fragment 1 + 2 (F1+2), and TF pathway inhibitor (TFPI). The gut bacteria composition, measured as gram-negative bacteria and diversity, was analysed in faecal samples. ResultsTriglycerides, FVIIa, and FVIIa-AT increased significantly after high-fat meals, whereas F1 + 2 decreased equally and significantly over time after both meals. There were no significant changes in TF and TFPI over time. The postprandial changes in F1 + 2 and TFPI after high-fat meals were negatively correlated with diversity. ConclusionsIncreased postprandial FVIIa is not accompanied by thrombin formation four hours after high-fat meals in patients with morbid obesity, possibly due to FVIIa-inhibition by AT.

Changes in the Gut Microbiota of Children with Autism Spectrum Disorder.

Alterations in the gut microbiota may influence gastrointestinal (GI) dysbiosis frequently reported in individuals with autism spectrum disorder (ASD). In this study, we sequenced the bacterial 16S rRNA gene to evaluate changes in fecal microbiota between 48 children with ASD and 48 healthy children in China. At the phylum level, the number of Firmicutes, Proteobacteria, and Verrucomicrobia decreased in children with ASD, while the Bacteroidetes/Firmicutes was significantly higher in autistic children due to enrichment of Bacteroidetes. At the genus level, the amount of Bacteroides, Prevotella, Lachnospiracea_incertae_sedis, and Megamonas increased, while Clostridium XlVa, Eisenbergiella, Clostridium IV, Flavonifractor, Escherichia/Shigella, Haemophilus, Akkermansia, and Dialister decreased in children with ASD relative to the controls. Significant increase was observed in the number of species synthesizing branched-chain amino acids (BCAAs), like Bacteroides vulgatus and Prevotella copri, while the numbers of Bacteroides fragilis and Akkermansia muciniphila decreased in children with ASD compared to the controls. Most importantly, the highest levels of pathogenic bacteria were different for each child with ASD in this cohort. We found that only one functional module, cellular antigens, was enriched in children with ASD, and other pathways like lysine degradation and tryptophan metabolism were significantly decreased in children with ASD. These findings provide further evidence of altered gut microbiota in Chinese ASD children and may contribute to the treatment of patients with ASD. LAY SUMMARY: This study characterized the gut bacteria composition of 48 children with ASD and 48 neurotypical children in China. The metabolic disruptions caused by altered gut microbiota may contribute significantly to the neurological pathophysiology of ASD, including significant increases in the number of species synthesizing BCAAs, and decreases in the number of probiotic species. These findings suggest that a gut microbiome-associated therapeutic intervention may provide a novel strategy for treating GI symptoms frequently seen in individuals with ASD. Autism Res 2020, 13: 1614-1625. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Seasonal dynamics and starvation impact on the gut microbiome of urochordate ascidian Halocynthia roretzi

BackgroundGut microbiota plays important roles in host animal metabolism, homeostasis and environmental adaptation. However, the interplay between the gut microbiome and urochordate ascidian, the most closet relative of vertebrate, remains less explored. In this study, we characterized the gut microbial communities of urochordate ascidian (Halocynthia roretzi) across the changes of season and starvation stress using a comprehensive set of omic approaches including 16S rRNA gene amplicon sequencing, shotgun metagenomics, metabolomic profiling, and transcriptome sequencing.ResultsThe 16S rRNA gene amplicon profiling revealed that ascidians harbor indigenous gut microbiota distinctly different to the marine microbial community and significant variations in composition and abundance of gut bacteria, with predominant bacterial orders representing each season. Depressed alpha-diversities of gut microbiota were observed across starvation stress when compared to the communities in aquafarm condition. Synechococcales involving photosynthesis and its related biosynthesis was reduced in abundance while the enrichments of Xanthomonadales and Legionellales may facilitate bile acid biosynthesis during starvation. Metabolomics analysis found that long chain fatty acids, linolenic acid, cyanoamino acid, and pigments derived from gut bacteria were upregulated, suggesting a beneficial contribution of the gut microbiome to the ascidian under starvation stress.ConclusionsOur findings revealed seasonal variation of ascidian gut microbiota. Defense and energy-associated metabolites derived from gut microbiome may provide an adaptive interplay between gut microbiome and ascidian host that maintains a beneficial metabolic system across season and starvation stress. The diversity-generating metabolisms from both microbiota and host might lead to the co-evolution and environmental adaptation.Graphical

Gut Microbiota-Polyphenol Interactions in Chicken: A Review.

Simple SummaryGut microbiota play crucial roles in digestion of feed and absorption of nutrients in fast growing chickens. Gut microbiota affects feed conversion ratio, body weight gain, apparent metabolizable energy, residual feed intake, and time taken to attain the desired weight, which have direct influence on the health and productivity of chickens. A normal gut microbiota is therefore very important for optimum health. Factors like the environment, heat stress, and housing conditions can cause detrimental changes in the gut resulting in poor health of birds and decreased production performance. Polyphenols can be used to improve gut health due to their established health benefits and strong antioxidant potential. The interaction between polyphenols and the gut microbiota further generates active metabolites, which can modulate the composition of the chicken gut microbiota. Because of the specificities of the gut microbiota-polyphenols interactions, current knowledge in this area is presented.The gastrointestinal tract of the chicken harbors very complex and diverse microbial communities including both beneficial and harmful bacteria. However, a dynamic balance is generally maintained in such a way that beneficial bacteria predominate over harmful ones. Environmental factors can negatively affect this balance, resulting in harmful effects on the gut, declining health, and productivity. This means modulating changes in the chicken gut microbiota is an effective strategy to improve gut health and productivity. One strategy is using modified diets to favor the growth of beneficial bacteria and a key candidate are polyphenols, which have strong antioxidant potential and established health benefits. The gut microbiota-polyphenol interactions are of vital importance in their effects on the gut microbiota modulation because it affects not only the composition of gut bacteria but also improves bioavailability of polyphenols through generation of more bioactive metabolites enhancing their health effects on morphology and composition of the gut microbiota. The object of this review is to improve the understanding of polyphenol interactions with the gut microbiota and highlights their potential role in modulation of the gut microbiota of chicken.

The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota

Elobixibat, a novel inhibitor of apical sodium-dependent bile acid transporter for treating chronic constipation, increases colonic bile acid concentrations, stimulating bowel function. However, it is not clear which bile acids are altered, or whether altered gut microbiota are associated with functional effects that may alter bowel function. To investigate the effects of elobixibat on changes in the faecal concentrations of total and individual bile acids and in faecal microbiota. This was a prospective, single-centre study. After baseline period, patients received 10mg daily of elobixibat for 2weeks. We evaluated the effects on bowel function, changes in faecal bile acid concentrations and composition of gut bacteria, before and after elobixibat administration. In the 30 patients analysed, the frequency of pre- and post-treatment bowel movements per fortnight was 7 and 10 (P<0.001), respectively. The pre-treatment faecal bile acid concentration increased significantly from 10.9 to 15.0µg/g stool post-treatment (P=0.030), with a significant increase in faecal deoxycholic acid (pre-treatment 3.94µg/g stool to post-treatment 5.02µg/g stool, P=0.036) and in glycine-conjugated deoxycholic and chenodeoxycholic acids. Shannon index was significantly decreased, but there were no significant changes at the genus and phylum levels. Short term treatment with elobixibat increased the concentrations of total bile acids and deoxycholic acid and decreased the diversity of faecal microbiota. The biological effects of elobixibat are associated with its effects on secretory bile acids, rather than the structural changes of an altered faecal microbiota.

Characterization of Spodoptera litura Gut Bacteria and Their Role in Feeding and Growth of the Host.

Insect gut microbes play important roles in host feeding, digestion, immunity, growth and development. Spodoptera litura is an important agricultural pest distributed of global importance. In the present study, diversity and functions of the gut bacteria in S. litura are investigated based on the approaches of metagenomics and denaturing gradient gel electrophoresis (DGGE). The results showed that the gut bacterial diversity of S. litura reared on taro leaves or an artificial diet, were similar at the phylum level, as both were mainly composed of Proteobacteria, but differed significantly at the order level. Spodoptera litura reared on taro leaves (Sl-tar) had gut biota mainly comprised of Enterobacteriales and Lactobacillales, while those reared on artificial diet (Sl-art) predominantly contained Pseudomonadales and Enterobacteriales, suggesting that gut bacteria composition was closely related to the insect’s diet. We found that feeding and growth of S. litura were significantly reduced when individuals were treated with antibiotics, but could be both restored to a certain extent after reimporting gut bacteria, indicating that gut bacteria are important for feeding, digestion, and utilization of food in S. litura. Metagenomic sequencing of gut microbes revealed that the gut bacteria encode a large number of enzymes involved in digestion, detoxification, and nutrient supply, implying that the gut microbes may be essential for improving the efficiency of food utilization in S. litura.

Thyroid-Gut-Axis: How Does the Microbiota Influence Thyroid Function?

A healthy gut microbiota not only has beneficial effects on the activity of the immune system, but also on thyroid function. Thyroid and intestinal diseases prevalently coexist—Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are the most common autoimmune thyroid diseases (AITD) and often co-occur with Celiac Disease (CD) and Non-celiac wheat sensitivity (NCWS). This can be explained by the damaged intestinal barrier and the following increase of intestinal permeability, allowing antigens to pass more easily and activate the immune system or cross-react with extraintestinal tissues, respectively. Dysbiosis has not only been found in AITDs, but has also been reported in thyroid carcinoma, in which an increased number of carcinogenic and inflammatory bacterial strains were observed. Additionally, the composition of the gut microbiota has an influence on the availability of essential micronutrients for the thyroid gland. Iodine, iron, and copper are crucial for thyroid hormone synthesis, selenium and zinc are needed for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients are often found to be deficient in AITDs, resulting in malfunctioning of the thyroid. Bariatric surgery can lead to an inadequate absorption of these nutrients and further implicates changes in thyroid stimulating hormone (TSH) and T3 levels. Supplementation of probiotics showed beneficial effects on thyroid hormones and thyroid function in general. A literature research was performed to examine the interplay between gut microbiota and thyroid disorders that should be considered when treating patients suffering from thyroid diseases. Multifactorial therapeutic and preventive management strategies could be established and more specifically adjusted to patients, depending on their gut bacteria composition. Future well-powered human studies are warranted to evaluate the impact of alterations in gut microbiota on thyroid function and diseases.

Composition and Diversity of Gut Bacteria Associated with the Eri Silk Moth, Samia ricini, (Lepidoptera: Saturniidae) as Revealed by Culture-Dependent and Metagenomics Analysis.

The polyphagous eri silk moth, Samia ricini, is associated with various symbiotic gut bacteria believed to provide several benefits to the host. The larvae of S. ricini were subjected to isolation of gut bacteria using culture-dependent 16S rRNA generic characterization, metagenomics analysis and qualitative enzymatic assays. Sixty culturable aerobic gut bacterial isolates comprising Firmicutes (54%) and Proteobacteria (46%); and twelve culturable facultative anaerobic bacteria comprising Proteobacteria (92%) and Firmicutes (8%) were identified inhabiting the gut of S. ricini. The results of metagenomics analysis revealed the presence of a diverse community of both culturable and un-culturable gut bacteria belonging to Proteobacteria (60%) and Firmicutes (20%) associated with seven orders. An analysis of the results of culturable isolation indicates that these bacterial isolates inhabited all the three compartments of the gut. Investigation on persistence of bacteria coupled with metagenomics analysis of the fifth instar suggested that bacteria persist in the gut across the different instar stages. In addition, enzymatic assays indicated that 48 and 75% of culturable aerobic, and 75% of anaerobic gut bacterial isolates had cellulolytic, lipolytic and nitrate reductase activities, thus suggesting that they may be involved in food digestion and nutritional provision to the host. These bacterial isolates may be good sources for profiling novel genes and biomolecules for biotechnological application.

Prebiotic Potential of Taro (Colocasia esculenta) to Modulate Gut Bacteria Composition and Short Chain Fatty Acid Production

Abstract Objectives Taro (Colocasia esculenta) is a high fiber tuber that holds cultural and agricultural importance in the Pacific. The high fiber content offers potential as a dietary prebiotic through the presence of resistant starch (RS). RS aids gut bacteria in the production of short-chain fatty acids (SCFA), which have health benefits to the host. As such, this study aimed to investigate the effect of taro on gut bacteria composition and SCFA production through in vitro human digestion and fecal fermentation methodology. Methods Five taro varieties (Bun Long, Mana Ulu, Moi, Kauai Lehua, Tahitian) were processed. RS concentration of taro was determined using Megazyme Resistant Starch kit. Taro samples were subjected to in vitro human digestion, replicating oral, gastric, small intestinal, and large intestinal phases. Digested taro samples were mixed with fresh human fecal slurries and fermented at 37°C for 24 hours. During fermentation, samples were collected at specific time points for analyzation of SCFA contents using gas chromatography and bacterial composition using 16S rRNA gene targeted amplicon sequencing. Results Tahitian variety had the highest RS concentration of 25.1%, with no significantly difference between Tahitian, Bun Long, and Moi varieties. All taro varieties exhibited statistically similar SCFA concentrations for 3-hydroxybutyric acid, acetic acid and propionic acid. Bun-Long, Tahitian, and Moi varieties exhibited significantly higher butyric acid levels than two other taro varieties. Butyric acid production had the highest correlation coefficient with RS concentration of 0.80. The bacterial community present in all taro varieties after 24 hours of fermentation was markedly different from that of the control communities, including shifts in both the Bacteriodes and Firmicutes phyla. Conclusions Different taro varieties have varying RS concentrations that affect the production of SCFA in an in vitro human digestion and fecal fermentation. The production of health-promoting butyric acid shows a strong positive correlation with the resistant starch concentration of taro. Taro distinctly causes shifts after 24 hours of fecal fermentation in Bacteriodes and Firmicutes phyla. These results provide new insights into the modulation of gut microbiota through dietary interventions. Funding Sources USDA-NIFA Hatch C-Maīki, University of Hawaii.

Investigation of Vitamin K Quinone Metabolism by Human Gut Bacteria

Abstract Objectives Vitamin K (VK) is a family of structurally-related quinones, phylloquinone (PK) and menaquinones (MKn, n = prenyl units in side chain), that share a common napthoquinone ring (menadione, MD). VK quinones function as an essential dietary nutrient for humans. MD is considered a pro-vitamin form of VK. Plants and bacteria that produce VK quinones (PK and MKn, respectively) use them as an electron carrier in energy production. Little is known about the interaction of dietary VK quinones with gut bacteria, which may be bi-directional. The objective of this study was to investigate the influence of VK quinones and MD on human gut bacteria composition and MKn production. Methods Stool from 5 healthy male donors was pooled and inoculated in bioreactors under conditions mimicking the colon (anaerobic, pH 6.8, 37°C) for 48 h. Bioreactors were treated with deuterium (2H)-labeled quinones (2H-PK, 2H-MK4, 2H-MK9 or 2H-MD); no quinones (cell controls); or 2H-quinone treatment with no stool (cell-free controls). Culture aliquots were collected at 0, 5, 10, 24, and 48 h, and separated into pellet and supernatant fractions. Experiments were conducted in triplicate. All fractions were analyzed for VK quinone content using LC-MS. DNA from 0 and 24 h pellet fractions was extracted and amplified for paired-end 16S sequencing on an Illumina MiSeq 2500. Differences in bacterial composition were assessed using PERMANOVA. Results Supplemented 2H-quinones accumulated in the pellet fraction over time. This was not observed in cell-free controls and was thus not a function of culture media solubility. Endogenous (unlabeled) production of MKn was unaffected by supplementation of 2H-quinones. Generated 2H-MKn (2H-MK4, 2H-MK9, 2H-MK10, and 2H-MK11) were only detected in 2H-MD supplemented vessels. Community-wide bacterial composition significantly differed between 0 h and 24 h (r2 = 0.85, P = 0.001), but not by quinone treatment. Conclusions PK and MKn, dietary viamin K quinones, were not transformed by gut microbes to MKn in vitro, whereas the pro-vitamin quinone MD was transformed to MKn of multiple side chain lengths. Although no quinone induced community-wide changes in bacteria composition, additional analyses are needed to assess species-specific growth promotion. Funding Sources USDA ARS and DOD Health Program.

Comparing Gut Microbiome in Mothers' Own Breast Milk- and Formula-Fed Moderate-Late Preterm Infants.

Gut microbiome plays an important role in adult human health and diseases. However, how nutritional factors shape the initial colonization of gut bacteria in infants, especially in preterm infants, is still not completely known. In this study, we compared the effects of feeding with mothers’ own breast milk (MBM) and formula on the initial composition and gene expression of gut bacteria in moderate–late preterm infants. Fecal samples were collected from ten formula-fed and ten MBM healthy infants born between 32 and 37 weeks’ gestation after they reached full-volume enteral feedings. Total DNAs were extracted from fecal samples for amplicon sequencing of 16S ribosomal RNA (rRNA) gene and total RNA with rRNA depletion for metatranscriptome RNA-Seq 16S rRNA gene amplicon sequencing results showed that the alpha-diversity was similar between the MBM- and formula-fed preterm infants, but the beta-diversity showed a significant difference in composition (p = 0.002). The most abundant taxa were Veillonella (18.4%) and Escherichia/Shigella (15.2%) in MBM infants, whereas the most abundant taxa of formula-fed infants were Streptococcus (18.6%) and Klebsiella (17.4%). The genera Propionibacterium, Streptococcus, and Finegoldia and order Clostridiales had significantly higher relative abundance in the MBM group than the formula group, whereas bacteria under family Enterobacteriaceae, genera Enterococcus and Veillonella, and class Bacilli were more abundant in the formula group. In general, microbiomes from both diet groups exhibited high functional levels of catalytic activity and metabolic processing when analyzed for gene ontology using a comparative metatranscriptome approach. Statistically, the microbial genes in the MBM group had an upregulation in expression related to glycine reductase, periplasmic acid stress response in Enterobacteria, acid resistance mechanisms, and L-fucose utilization. In contrast, the formula-fed group had upregulations in genes associated with methionine and valine degradation functions. Our data suggest that the nutritional source plays a role in shaping the moderate–late preterm gut microbiome as evidenced by the differences in bacterial composition and gene expression profiles in the fecal samples. The MBM group enriched Propionibacterium. Glycine reductase was highly upregulated in the microbiota from MBM along with the upregulated acid stress tolerance genes, suggesting that the intensity of fermentation process was enhanced.

Gut fungal dysbiosis and altered bacterial-fungal interaction in patients with diarrhea-predominant irritable bowel syndrome: An explorative study.

Little is known about intestinal fungi in IBS patients whose gut bacteria have been investigated a lot. In order to explore causal relationship between IBS and gut mycobiome, and use gut fungi to diagnose or even treat IBS, further characterization of it in IBS is required. Fifty-five diarrhea-predominant IBS (D-IBS) patients fulfilling Rome III criteria, and 16 healthy controls (HC) were recruited. Fresh fecal samples were collected and used for 16s rRNA and ITS2 high-throughput sequencing. Diversity and composition of gut bacteria and fungi, as well as bacterial-fungal interactions in D-IBS patients, were characterized. Specific fungal taxa differentiating D-IBS from HC were recognized by LEfSe and RandomForest methods, and their association with clinical symptoms was assessed by Spearman's correlation. Diarrhea-predominant irritable bowel syndrome patients showed abnormal (IBS-dysbiosis) or normal (HC-like IBS) fecal bacterial structure and diversity compared with healthy controls. However, fecal fungal signatures differed absolutely between D-IBS and HC, which indicated a more susceptible alteration of gut fungi than bacteria in D-IBS. Fecal fungi showed significant correlations with IBS symptoms, especially Mycosphaerella, Aspergillus, Sporidiobolus, and Pandora which were identified to potentially differentiate D-IBS from HC. Moreover, compared with HC there were markedly declined bacterial-fungal interactions in D-IBS, in which Candida changed from negative to positive correlations with bacteria, and Eurotium changed from positive correlations to irrelevance, while Debaryomyces gained negative correlations with bacteria. Gut fungal dysbiosis and altered bacterial-fungal interactions were present in patients with D-IBS, and gut fungi could be used to diagnose D-IBS.

SUN-LB94 Impact of the Gut Microbiome and Renin-Angiotensin-Aldosterone System in Hypertensive Patients With Low-Salt Intake

Salt intake is one of most important environmental factors responsible for triggering the onset of hypertension. Renin-angiotensin-aldosterone system (RAAS) plays a key role in adjusting sodium homeostasis and blood pressure. Recently, the potential role of the gut microbiome (GM) in altering the health of the host has drawn considerable attention. We investigated the impact of intestinal microflora and RAAS in hypertensive patients with low-salt or high-salt intake using an observational study.A total of 239 participants were enrolled and their GMs and clinical backgrounds examined, including the renin-angiotensin-aldosterone system and inflammatory cytokine levels. On the basis of enterotypes—determined by cluster analysis—and salt intake, the participants were classified into four groups, low salt/GM enterotype 1, low salt/GM enterotype 2, high salt/GM enterotype 1, and high salt/GM enterotype 2.The prevalence of hypertension was significantly lower in the low-salt intake (low salt/GM enterotype 1 = 47% vs low salt/GM enterotype 2 = 27%, p = 0.04) groups. No significant difference in the prevalence of hypertension was observed for the two GM enterotype groups with high-salt intake (GM enterotype 1 = 50%, GM enterotype 2 = 47%; p = 0.83). Plasma aldosterone concentration was significantly different among the four groups (p < 0.01). Furthermore, the relative abundance of Blautia, Bifidobacterium, Escherichia-Shigella, Lachnoclostridium, and Clostridium sensu stricto was also significantly different among these enterotypes. This suggested in certain individuals (with specific gut bacteria composition) changing dietary habits—to low salt—would be ineffective for regulating hypertension through RAAS. Our findings provide a new strategy for controlling blood pressure and preventing the development of hypertension through restoring GM homeostasis.

Gut Bacteria Composition Drives Primary Resistance to Cancer Immunotherapy in Renal Cell Carcinoma Patients

BackgroundThe development of immune checkpoint blockade (ICB) has revolutionized the clinical outcome of renal cell carcinoma (RCC). Nevertheless, improvement of durability and prediction of responses remain unmet medical needs. While it has been recognized that antibiotics (ATBs) decrease the clinical activity of ICB across various malignancies, little is known about the direct impact of distinct intestinal nonpathogenic bacteria (commensals) on therapeutic outcomes of ICB in RCC. ObjectiveTo evaluate the predictive value of stool bacteria composition for ICB efficacy in a cohort of advanced RCC patients. Design, setting, and participantsWe prospectively collected fecal samples from 69 advanced RCC patients treated with nivolumab and enrolled in the GETUG-AFU 26 NIVOREN microbiota translational substudy phase 2 trial (NCT03013335) at Gustave Roussy. We recorded patient characteristics including ATB use, prior systemic therapies, and response criteria. We analyzed 2994 samples of feces from healthy volunteers (HVs). In parallel, preclinical studies performed in RCC-bearing mice that received fecal transplant (FMT) from RCC patients resistant to ICB (NR-FMT) allowed us to draw a cause-effect relationship between gut bacteria composition and clinical outcomes for ICB. The influence of tyrosine kinase inhibitors (TKIs) taken before starting nivolumab on the microbiota composition has also been assessed. Outcome measurements and statistical analysisMetagenomic data (MG) from whole genome sequencing (WGS) were analyzed by multivariate and pairwise comparisons/fold ratio to identify bacterial fingerprints related to ATB or prior TKI exposure and patients’ therapeutic response (overall response and progression-free survival), and compared with the data from cancer-free donors. Results and limitationsRecent ATB use (n = 11; 16%) reduced objective response rates (from 28% to 9%, p < 0.03) and markedly affected the composition of the microbiota, facilitating the dominance of distinct species such as Clostridium hathewayi, which were also preferentially over-represented in stools from RCC patients compared with HVs. Importantly, TKIs taken prior to nivolumab had implications in shifting the microbiota composition. To establish a cause-effect relationship between gut bacteria composition and ICB efficacy, NR-FMT mice were successfully compensated with either FMT from responding RCC patients or beneficial commensals identified by WGS-MG (Akkermansia muciniphila and Bacteroides salyersiae). ConclusionsThe composition of the microbiota is influenced by TKIs and ATBs, and impacts the success of immunotherapy. Future studies will help sharpen the role of these specific bacteria and their potential as new biomarkers. Patient summaryWe used quantitative shotgun DNA sequencing of fecal microbes as well as preclinical models of fecal or bacterial transfer to study the association between stool composition and (pre)clinical outcome to immune checkpoint blockade. Novel insights into the pathophysiological relevance of intestinal dysbiosis in the prognosis of kidney cancer may lead to innovative therapeutic solutions, such as supplementation with probiotics to prevent primary resistance to therapy.

High l-Carnitine Ingestion Impairs Liver Function by Disordering Gut Bacteria Composition in Mice.

This article studied the effects of high l-carnitine consumption on intestinal microbiota, liver function, and metabolite distribution in mice. 16S rRNA results showed that high l-carnitine supplementation could induce the accumulation of Anaerobiospirillum, Coriobacteriaceae, Akkermansia_muciniphila, and Helicobacter. High intake of l-carnitine also induced liver injury, which was proved by the increases in the serum AST and ALT activities, production of inflammatory liver cytokines (IL-1, IL-6, TNF-α, and TNF-β), lipid metabolism (TC, TG, HDL, and LDL) disorder, and decline in antioxidant ability (SOD, GSH-Px, MDA, and RAHFR). The correlation analysis results showed that Anaerobiospirillum, Akkermansia_muciniphila, and Helicobacter were strongly positively correlated with AST, IL-1, TNF-α, TNF-β, and MDA levels (r > 0.5, p < 0.01 or p < 0.05). All in all, high l-carnitine ingestion could induce a decline in the liver function by disorder in the gut bacteria composition, resulting in an increase in TMAO metabolism.

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis-induced depressive-like behaviors in mice.

Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP). Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria. EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation. Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.

Technical and Theoretic Limitations of the Experimental Evidence Supporting a Gut Bacterial Etiology in Mental Illness

The impact of gut bacteria on the brain and behavior has become the subject of intense research. The brain is sensitive to biochemical and physiologic changes in the body, for example, changes in blood oxygenation or nutritional status. The collection of microorganisms residing within the digestive tract (the gut microbiome) is increasingly considered a major contributor to human physiology. These 2 considerations have led to the hypothesis that human psychology, including complex constructs like emotion and mental illness, could be influenced by the composition or function of gut bacteria. Five lines of evidence have been used to support the concept, including human correlational research, probiotic supplementation, antibiotic use, germ-free animal research, and fecal transplantation. Results from these experiments do not provide substantial support for the theory that complex human psychology is under the influence of gut bacteria. Placebo-controlled interventional research in humans, in particular fecal microbiota transplantation, will be required before a stronger conclusion can be reached.

The environment and species affect gut bacteria composition in laboratory co-cultured Anopheles gambiae and Aedes albopictus mosquitoes

The midgut microbiota of disease vectors plays a critical role in the successful transmission of human pathogens. The environment influences the microbiota composition; however, the relative mosquito-species contribution has not been rigorously disentangled from the environmental contribution to the microbiota structure. Also, the extent to which the microbiota of the adult sugar food source and larval water can predict that of the adult midgut and vice versa is not fully understood. To address these relationships, larvae and adults of Anopheles gambiae and Aedes albopictus were either reared separately or in a co-rearing system, whereby aquatic and adult stages of both species shared the larval water and sugar food source, respectively. Despite being reared under identical conditions, clear intra- and interspecies differences in midgut microbiota-composition were observed across seven cohorts, collected at different time points over a period of eight months. Fitting a linear model separately for each OTU in the mosquito midgut showed that two OTUs significantly differed between the midguts of the two mosquito species. We also show an effect for the sugar food source and larval water on the adult midgut microbiota. Our findings suggest that the mosquito midgut microbiota is highly dynamic and controlled by multiple factors.

Effects of physical activity in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease is the most common liver disease worldwide. The patomechanism is unknown, but unhealthy diet, high caloric and carbohydrate intake, physical inactivity play important role in the pathomechanism. Lifestyle modification, physical activity are regarded as a foundation for the management of nonalcoholic fatty liver disease. Several tests have proved the beneficial effect of regular exercising on the histological differences of the liver tissue. Exercising also improves the sensitivity against insulin, increases lipogenesis and carbohydrate metabolism, at the same time the chance for steatosis and fibrosis decreases. Moreover, as a result of regular exercising the visceral fat tissue also decreases, which plays an important role in the inflammatory process and fibrogenesis of the liver. The alteration of the gut bacteria composition might also contribute to the positive changes in the liver. The lifestyle of everyday people nowadays, however, does not favour physical activity. Most people cannot or do not want to accept these facts. First and foremost, patients must be persuaded of the necessity of the change in their habits. Adequate physical activity in itself makes it possible that even without a diet liver disease can be prevented. Orv Hetil. 2020; 161(6): 203-207.

Dietary Patterns Are Associated with Serum Metabolite Patterns and Their Association Is Influenced by Gut Bacteria among Older German Adults

ABSTRACTBackgroundAlthough dietary intakes and dietary intake patterns (DPs) have been associated with single metabolites, it is unclear whether DPs are also reflected in specific metabolite patterns (MPs). Moreover, the influence of groups of gut bacteria on the relationship between DPs and MPs is underexplored.ObjectivesWe aimed to investigate the association of DPs and serum MPs and also the modifying effect of the gut bacteria compositional patterns (BCPs).MethodsThis is a cross-sectional investigation among 225 individuals (median age: 63 y; 53% women) from the European Prospective Investigation into Cancer and Nutrition study. Dietary intakes were assessed by three 24-h dietary recalls, gut bacteria composition was quantified by 16S rRNA gene sequencing, and the serum metabolome was profiled by an untargeted approach. We identified DPs and BCPs by the treelet transform analysis. We modeled associations between DPs and 8 previously published MPs and the modifying effect of BCPs by fitting generalized linear models using DataSHIELD R.ResultsWe identified 5 DPs and 7 BCPs. The “bread, margarine, and processed meat” and “fruiting vegetables and vegetable oils” DPs were positively associated with the “amino acids” (β = 0.35; 95% CI: 0.02, 0.69; P = 0.03) and “fatty acids” MPs (β = 0.45; 95% CI: 0.16, 0.74; P = 0.01), respectively. The “tea and miscellaneous” was inversely associated with the “amino acids” (β = −0.28; 95% CI: −0.52, −0.05; P = 0.02) and “amino acid derivatives” MPs (β = −0.21; 95% CI: −0.39, −0.02; P = 0.03). One BCP negatively modified the association between the “bread, margarine, and processed meat” DP and the “amino acids” MP (P-interaction = 0.01).ConclusionsIn older German adults, DPs are reflected in MPs, and the gut bacteria attenuate 1 DP–MP association. These MPs should be explored as biomarkers of these jointly consumed foods while taking into account a potentially modifying role of the gut bacteria.