Exercise for the Diabetic Gut—Potential Health Effects and Underlying Mechanisms

It can be assumed that changes in the gut microbiota play a crucial role in the development of type 2 diabetes mellitus (T2DM). It is generally accepted that regular physical activity is beneficial for the prevention and therapy of T2DM. Therefore, this review analyzes the effects of exercise training on the gut microbiota composition and the intestinal barrier function in T2DM. The current literature shows that regular exercise can influence the gut microbiota composition and the intestinal barrier function with ameliorative effects on T2DM. In particular, increases in the number of short-chain fatty acid (SCFA)-producing bacteria and improvements in the gut barrier integrity with reduced endotoxemia seem to be key points for positive interactions between gut health and T2DM, resulting in improvements in low-grade systemic inflammation status and glycemic control. However, not all aspects are known in detail and further studies are needed to further examine the efficacy of different training programs, the role of myokines, SCFA-producing bacteria, and SCFAs in the relevant metabolic pathways. As microbial signatures differ in individuals who respond differently to exercise training programs, one scientific focus could be the development of computer-based methods for the personalized analysis of the gut microbiota in the context of a microbiota/microbiome-based training program.     

Black Raspberries and Their Anthocyanin and Fiber Fractions Alter the Composition and Diversity of Gut Microbiota in F-344 Rats

Natural compounds can alter the diversity and composition of the gut microbiome, potentially benefiting our health. We previously demonstrated chemopreventive effects of black raspberries (BRBs) in colorectal cancer, which is associated with gut dysbiosis. To investigate the effects of whole BRBs and their fractions on gut microbiota, we fed F-344 rats a control diet, 5% BRBs, the BRB anthocyanin fraction, or the BRB residue fraction for 6 weeks. Feces were collected at baseline and at weeks 3 and 6, and bacterial sequence counts were analyzed. We observed distinct patterns of microbiota from different diet groups. Beta diversity analysis suggested that all diet groups exerted time-dependent changes in the bacterial diversity. Hierarchical clustering analysis revealed that post-diet fecal microbiota was segregated from baseline fecal microbiota within each diet. It is interesting to note that fractions of BRBs induced different changes in gut bacteria compared to whole BRBs. The abundance of specific microbial species known to have anti-inflammatory effects, such as Akkermansia and Desulfovibrio, was increased by whole BRBs and their residue. Further, butyrate-producing bacteria, e.g., Anaerostipes, were increased by whole BRBs. Our results suggest that whole BRBs and their fractions alter the gut microbiota in ways that could significantly influence human health.     

口腔菌群影响因素及其与上消化道肿瘤关联研究进展

人体口腔微生物种类复杂且数目庞大,其构成及分布可受到多种因素的影响。随着宏基因组学技术的发展,口腔菌群在肿瘤发生发展中的重要作用逐渐受到广泛关注。本文通过检索PubMed、Embase、中国知网、万方数据知识服务平台等数据库,对口腔菌群的影响因素及其与口腔癌、食管癌、胃癌关联的研究现况进行了总结,发现口腔菌群可受到性别、年龄、种族和生活习惯等多种因素影响,特定口腔菌群与上消化道肿瘤的发病风险相关,具有作为上消化道肿瘤初筛标志物的潜能。本文通过综述口腔菌群的影响因素及其与上消化道肿瘤关联性研究进展,旨在为探索上消化道肿瘤病因提供微生物组学的新方向,为优化、完善上消化道肿瘤高危人群的早期筛查及早诊早治方案提供科学依据。     

The human gut flora in nutrition and approaches for its dietary modulation

Concepts about human nutrition have changed significantly during the past few decades, especially in the developed world. There is a shift from the concept of ‘adequate’ to ‘optimal’ nutrition. Thus, diet is not only considered as a means of survival but also as a way of achieving better health and quality of life. The human colonic microbiota has a central role in both health and nutrition. It is unique in complexity and function in the body. More than 500 different bacterial species inhabit the human gut, some considered beneficial, others benign, and others detrimental to host health. There is a delicate balance between the host and the colonic microflora, which not only acts as a protective barrier against infection, but also provides up to 7–10% of the host's daily energy requirements through the fermentation of carbohydrates that escape digestion in the upper gastrointestinal tract. Functional foods targeting the colon focus on the development and prevalence of bacterial species that are considered beneficial to human health, namely, bifidobacteria and lactobacilli. Three approaches for the modulation of human gut flora are reviewed here: probiotics, prebiotics and synbiotics, along with methods for improved characterization and analysis of the intestinal microbiota.     

Scalp microbiota alterations in children with pediculosis

Pediculosis is a disease caused by the insect Pediculus humanus capitis that mainly occurs in childhood. A comparative study was carried out evaluating groups of schoolchildren with (group A) and without pediculosis (group B) to analyse the characteristics of the scalp microbiota. Samples were collected by swab using Stuart transport medium and incubate in Sabouraud dextrose agar with tetracycline to analyse the fungal microbiota and in blood agar to assess the bacterial microbiota. The isolates identity was confirmed by sequencing of the 16S and 18S regions of the ribosomal DNA gene for bacteria and fungi, respectively. The analysis of the 186 isolates led to the identification of 35 bacteria and 40 fungi in group A and 47 bacteria and 64 fungi in group B. The results indicate differences in bacterial and fungal species in the groups analysed. In the observed bacterial microbiota, Staphylococcus capitis occurred more frequently than Staphylococcus epidermidis in group A vs B. Among fungal isolates, Debaryomyces sp. was more frequent in group B vs A. Our findings showed scalp microbiota alterations in children with pediculosis, meriting future studies to analyse the relationship between these agents and their impact on human health.     

Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric‐Onset Intestinal Failure

Background: Intestinal failure (IF)–associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. Methods: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture‐independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. Results: Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. Conclusions: Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.     

The Origin of Human Milk Bacteria: Is There a Bacterial Entero-Mammary Pathway during Late Pregnancy and Lactation?

Human milk is a source of bacteria to the infant gut; however, the origin of milk bacteria, as well as their impact on neonatal gut microbiota establishment, remains largely unknown. In the past years, results provided by different research groups suggest that certain bacteria from the maternal gastrointestinal tract could translocate through a mechanism involving mononuclear immune cells, migrate to the mammary glands via an endogenous cellular route (the bacterial entero-mammary pathway), and subsequently colonize the gastrointestinal tract of the breast-fed neonate. If such findings are confirmed in the future, we could exert a positive influence on infant health by modulating the maternal gut microbiota.     

Reduced Abundance of Nitrate-Reducing Bacteria in the Oral Microbiota of Women with Future Preeclampsia

The oral microbiota can contribute to the regulation of blood pressure by increasing the availability of nitric oxide through the reduction of nitrate to nitrite, which can be converted into nitric oxide in the stomach and then enter the circulation. It is unclear if the composition of the oral microbiota is different between women who do and do not develop preeclampsia. This study aimed to compare the composition of the buccal microbiota just prior to the development of symptoms at 36 weeks gestation in 12 women who developed late-onset preeclampsia and 24 matched women who remained normotensive throughout pregnancy by 16S rRNA gene amplicon sequencing. The abundance of the nitrate-reducing Veillonella spp V. parvula and V. dispar and a subunit of nitrate reductase narH was compared using real-time PCR. The abundance of bacteria was correlated with maternal blood pressure and dietary intake of nitrate-containing vegetables. The results showed that the abundance of nitrate-reducing bacteria including Veillonella, specifically V. parvula, and Prevotella was reduced in women who developed preeclampsia. Veillonella but not Prevotella abundance was negatively correlated with maternal blood pressure. The dietary intake of nitrate-containing vegetables did not differ between the groups and was not correlated with the abundance of Veillonella. There was no difference in the abundance of the nitrate reductase subunit narH between the groups. These results suggest that the abundance of nitrate-reducing bacteria is reduced in the oral microbiota of women who later develop preeclampsia, indicating a potential pathway for prevention.     

Comparison of standard and immune-enhancing oral formulas in asymptomatic HIV-infected persons: a multicenter randomized controlled clinical trial

BACKGROUND: Both standard and immune-enhancing oral formulas are widely used to forestall HIV wasting and to promote immune function. However, there is little scientific evidence to support the differential effects of these formulas in asymptomatic HIV disease. The aim of this study was to compare the effects of an immune-enhancing oral formula and a standard oral formula on nutrition and immune measures in asymptomatic HIV-infected persons. A secondary aim was to evaluate the feasibility of maintaining a diverse sample of outpatients on a long-term oral formula protocol. METHODS: In this multicenter controlled nonblinded study, 90 asymptomatic HIV-infected persons with CD4 cell counts between 275 and 550 cells/mm3 were randomized to a control group; a standard oral formula group (Ensure Plus); or an immune-enhancing oral formula group (Advera). All groups received basic nutrition counseling. Participants were evaluated on nutrition, immune, and feasibility measures at 3-month intervals during the 12-month study period. Differences in nutrition and immune measures among the 3 groups were analyzed using the Kruskal-Wallis and Wilcoxon tests. Wilcoxon tests and correlation coefficients were used to analyze feasibility data. RESULTS: Sixty-six outpatients completed the 12-month study protocol. Among the 3 groups, there were no significant differences with respect to body weight, bioelectrical impedance analysis (BIA)-derived body cell and fat mass, daily caloric intake, and serum albumin at any of the study visits. Moreover, absolute CD4+ T lymphocytes and percentages did not significantly differ at any time point among the 3 groups. Acceptability and tolerance of the formulas were high for both the standard and immune-enhancing oral formula groups. CONCLUSIONS: Within the context and limitations of this study, standard and immune-enhancing oral formulas consumed daily for 1 year had no differential effects on nutrition or immune parameters in asymptomatic HIV-infected persons.     

Role of Probiotics in Modulating Human Gut Microbiota Populations and Activities in Patients with Colorectal Cancer—A Systematic Review of Clinical Trials

Background: Growing attention has been given to the role of nutrition and alterations of microbial diversity of the gut microbiota in colorectal cancer (CRC) pathogenesis. It has been suggested that probiotics and synbiotics modulate enteric microbiota and therefore may be used as an intervention to reduce the risk of CRC. The aim of this study was to evaluate the influence of probiotics/synbiotics administration on gut microbiota in patients with CRC. Methods: PubMed, Scopus, and Web of Science were searched between December 2020 and January 2021. Randomized controlled trials (RCTs) recruiting adults with CRC, who have taken probiotics/synbiotics for at least 6 days were included. Changes in gut microbiota and selected biochemical and inflammatory parameters (i.e., hsCRP, IL-2, hemoglobin) were retrieved. Results: The search resulted in 198 original research articles and a final 6 were selected as being eligible, including 457 subjects. The median age of patients was 65.4 years old and they were characterized by the median BMI value: 23.8 kg/m². The literature search revealed that probiotic/synbiotic administration improved enteric microbiota by increasing the abundance of beneficial bacteria such as Lactobacillus, Eubacterium, Peptostreptococcus, Bacillus and Bifidobacterium, and decreased the abundance of potentially harmful bacteria such as Fusobacterium, Porhyromonas, Pseudomonas and Enterococcus. Additionally, probiotic/synbiotic intervention improved release of antimicrobials, intestinal permeability, tight junction function in CRC patients. Conclusions: The use of probiotics/synbiotics positively modulates enteric microbiota, improves postoperative outcomes, gut barrier function and reduces inflammatory parameters in patients suffering from CRC.     

Fructooligosaccharides and fiber partially prevent the alterations in fecal microbiota and short-chain fatty acid concentrations caused by standard enteral formula in healthy humans

The intestinal microbiota are important during enteral tube feeding because they exert colonization resistance and produce SCFAs. However, the effect of the enteral formula composition on major bacterial groups of the microbiota has not been clearly defined. The aim of this study was to investigate the effect of enteral formulas with and without prebiotic fructooligosaccharides (FOS) and fiber on the fecal microbiota and SCFAs. Healthy subjects (n = 10; 4 men, 6 women) consumed both a standard enteral formula and one containing FOS (5.1 g/L) and fiber (8.9 g/L) as a sole source of nutrition for 14 d in a randomized, double-blind, crossover trial with a 6-wk washout phase. Fecal samples were collected at the start and end of each formula phase, and were analyzed for major bacterial groups and SCFA concentrations using fluorescent in situ hybridization and GLC, respectively. Although there were reductions in total fecal bacteria due to both formula treatments, concentrations were higher after the FOS/fiber formula period compared with the standard formula period (11.2 +/- 0.2 vs. 11.0 +/- 0.2 log(10) cells/g, P = 0.005). The FOS/fiber formula increased bifidobacteria (P = 0.004) and reduced clostridia (P = 0.006). Compared with the standard formula, the FOS/fiber formula resulted in higher concentrations of total SCFA (332.4 +/- 133.8 vs. 220.1 +/- 124.5 micromol/g, P = 0.022), acetate (219.6 +/- 96.3 vs. 136.8 +/- 74.5 micromol/g, P = 0.034) and propionate (58.4 +/- 37.4 vs. 35.6 +/- 25.5 micromol/g, P = 0.02). This study demonstrates that standard enteral formula leads to adverse alterations to the fecal microbiota and SCFA concentrations in healthy subjects, and these alterations are partially prevented by fortification of the formula with FOS and fiber.     

Changes in Composition of Caecal Microbiota Associated with Increased Colon Inflammation in Interleukin-10 Gene-Deficient Mice Inoculated with Enterococcus Species

Human inflammatory bowel disease (IBD) is a chronic intestinal disease where the resident microbiota contributes to disease development, yet the specific mechanisms remain unclear. Interleukin-10 gene-deficient (Il10^-/-) mice develop inflammation similar to IBD, due in part to an inappropriate response to commensal bacteria. We have previously reported changes in intestinal morphology and colonic gene expression in Il10^-/- mice in response to oral bacterial inoculation. In this study, we aimed to identify specific changes in the caecal microbiota associated with colonic inflammation in these mice. The microbiota was evaluated using pyrotag sequencing, denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR. Microbiota profiles were influenced by genotype of the mice and by bacterial inoculation, and a strong correlation was observed between the microbiota and colonic inflammation scores. Although un-inoculated Il10^-/- and C57 mice had similar microbiota communities, bacterial inoculation resulted in different changes to the microbiota in Il10^-/- and C57 mice. Inoculated Il10^-/- mice had significantly less total bacteria than un-inoculated Il10^-/- mice, with a strong negative correlation between total bacterial numbers, relative abundance of Escherichia/Shigella, microbiota diversity, and colonic inflammation score. Our results show a putative causative role for the microbiota in the development of IBD, with potentially key roles for Akkermansia, or for Bacteroides, Helicobacter, Parabacteroides, and Alistipes, depending on the composition of the bacterial inoculum. These data support the use of bacterially-inoculated Il10^-/- mice as an appropriate model to investigate human IBD.     

Postbiotic Supplementation for Children and Newborn’s Health

It is now well known how the microbiota can positively or negatively influence humans health, depending on its composition. The microbiota’s countless beneficial effects have allowed it to be defined as a genuine symbiont for our species. In an attempt to positively influence the microbiota, research has focused on probiotics and prebiotics. Probiotics are viable beneficial bacteria of various strains. Prebiotics are specific substances able to favor the development of advantageous bacteria strains. Postbiotics are a new category of compounds capable of affecting the microbiota. According to the different definitions, postbiotics include both nonviable bacteria and substances deriving from bacterial metabolism. Postbiotics are particularly promising in pediatric settings, as they offer some advantages over probiotics, including the absence of the risk of intestinal translocation or worsening of local inflammation. For these reasons, their use in fragile population categories such as newborns, and even more prematures, seems to be the best solution for improving microbiota’s health in this population. This narrative review aims to collect the research conducted so far on postbiotics’ potential in the first stages of life.     

A Crosstalk between Diet,Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.     

Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) for microbiome studies: bacterial diversity in the ileum of newly weaned Salmonella-infected pigs

The microbiota of an animal's intestinal tract plays a vital role in the animal's overall health. There is a surprising scarcity of information on the microbial diversity in the gut of livestock species such as cattle and swine. Here we describe a bacterial 16S-based tag-encoded FLX amplicon pyrosequencing (bTEFAP) method that we have developed as a high-throughput universal tool for bacterial diversity, epidemiology, and pathogen detection studies. This method will allow hundreds of samples to be run simultaneously but analyzed individually or as groups. To test this new methodology, we individually evaluated the bacterial diversity in the ileum of 21 pigs. Ubiquitous bacteria detected in the newly weaned pigs were Clostridium spp., Lactobacillus spp., and Helicobacter spp. Many of the pigs had surprisingly low concentrations of beneficial bacteria such as Bifidobacterium spp. Only four of the pigs were shown to be positive for Salmonella spp. using traditional culture methods. A total of eight pigs were bTEFAP positive for Salmonella spp., including all four of the pigs that had been culture positive. Two of the pigs sampled were also positive for Campylobacter spp. tentative identified as jejuni. Using rarefaction curves modeled with the Richards equation, we estimated the maximum number of unique species level (3% dissimilarity) operational taxonomic units in the ileum of these pigs. These predictions indicated that there may be as many as 821 different species associated with the ileum in pigs. Together these data indicate a powerful potential of this technology in food safety and epidemiological and bacterial diversity applications. Using bTEFAP, we can expect to gain a better understanding of how the microbiome of an animal contributes to its health and well-being.     

大鼠肠缺血-再灌注后营养对肠黏膜屏障功能的影响

目的:研究不同营养物质及营养支持途径对大鼠肠道缺血-再灌注时肠黏膜屏障功能的影响. 方法:将大鼠随机分为缺血-再灌注组、对照组及缺血-再灌注后各营养支持组.实验结束行肠黏膜屏障功能指标的检测. 结果:缺血-再灌注后肠黏膜发生明显损伤,普通肠外营养(PN)组D-乳酸、血浆内毒素水平、细菌移位率均显著高于其他各组(P<0.05);普通肠内营养(EN)组血浆内毒素水平明显低于谷氨酰胺肠外营养(G-PN)组(P<0.05),EN和免疫肠内营养(IEN)组细菌移位率无显著差异(P>0.05). 结论:①肠内营养在维护肠黏膜屏障功能方面优于肠外营养.②谷氨酰胺对改善肠黏膜屏障功能有显著作用,但无法取代肠内营养的作用.③免疫增强型营养与普通肠内营养相比,对细菌移位的防治效果并不大.     

Molecular analysis of yogurt containing Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus in human intestinal microbiota

BACKGROUND: Yogurt has traditionally been considered a probiotic-carrier food with health-promoting effects. Despite the universal assumption of this assertion, several researchers have evaluated the real capability of the yogurt bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus to survive and proliferate in the human intestine and have found contradictory results. OBJECTIVE: This double-blind crossover study assessed the qualitative and quantitative effects of fresh and heat-treated yogurt on bacterial intestinal microbiota from healthy subjects. DESIGN: The subjects were divided into experimental (n=63) and control (n=16) groups. The experimental group consumed fresh and heat-treated yogurt for 15 d according to a crossover design with a washout period of 2 wk. Three different fecal samples per individual were recovered: at baseline, after fresh yogurt intake, and after heat-treated yogurt intake. Qualitative changes in microbiota were studied by denaturing gel gradient electrophoresis (DGGE) with universal and lactic acid bacteria (LAB) 16S-rRNA primers. Quantitative changes in LAB, Clostridium coccoides, Clostridium perfringens, and Bacteroides groups were analyzed by real-time polymerase chain reaction. RESULTS: A particular DGGE stable band pattern was observed in each sample. No significant qualitative differences were detected in any fecal sample. However, a significantly higher density of LAB and C. perfringens and a significant decrease in the density of Bacteroides was observed after consumption of both types of yogurt. Microbiota density was not significantly different between the fresh and heat-treated yogurt groups, except for LAB, which was significantly greater in the fresh yogurt group. CONCLUSION: The main change in human microbiota observed after yogurt consumption was an increase in the density of LAB and C. perfringens to the detriment of Bacteroides. Bacterial changes were not different after the consumption of fresh and heat-treated yogurt.     

肠道菌群功能研究进展

人体中寄居着大量的微生物,即共生菌群,这些菌群的基因总和称为微生物组。存在于人体中的各种菌群和微生物组对人体的健康和疾病发挥着重要作用。正常情况下肠道菌群与人体处于共生关系,具有防御外源性感染、促进免疫系统的成熟与平衡、营养与代谢等生理功能。肠道共生菌群的紊乱则与许多疾病有关,包括过敏性疾病、自身免疫性疾病、代谢性疾病、细菌感染和结肠癌等。     

Potential Effects of Sucralose and Saccharin on Gut Microbiota: A Review

Artificial sweeteners are additives widely used in our diet. Although there is no consensus, current evidence indicates that sucralose and saccharin could influence the gut microbiota. The aim of this study was to analyze the existing scientific evidence on the effects of saccharin and sucralose consumption on gut microbiota in humans. Different databases were used with the following search terms: sweeteners, non-caloric-sweeteners, sucralose, splenda, saccharin, sugartwin, sweet’n low, microbiota, gut microbiota, humans, animal model, mice, rats, and/or in vitro studies. In vitro and animal model studies indicate a dose-dependent relationship between the intake of both sweeteners and gut microbiota affecting both diversity and composition. In humans, long-term study suggests the existence of a positive correlation between sweetener consumption and some bacterial groups; however, most short-term interventions with saccharin and sucralose, in amounts below the ADI, found no significant effect on those groups, but there seems to be a different basal microbiota-dependent response of metabolic markers. Although studies in vitro and in animal models seem to relate saccharin and sucralose consumption to changes in the gut microbiota, more long-term studies are needed in humans considering the basal microbiota of participants and their dietary and lifestyle habits in all population groups. Toxicological and basal gut microbiota effects must be included as relevant factors to evaluate food safety and nutritional consequences of non-calorie sweeteners. In humans, doses, duration of interventions, and number of subjects included in the studies are key factors to interpret the results.