Intestinal Bifidobacteria Research Articles

Molecular cross-talk among human intestinal bifidobacteria as explored by a human gut model.

Bifidobacteria are well known as common and abundant colonizers of the human gut and are able to exert multiple beneficial effects on their host, although the cooperative and competitive relationships that may occur among bifidobacterial strains are still poorly investigated. Therefore, to dissect possible molecular interactions among bifidobacterial species that typically colonize the human gut, three previously identified bifidobacterial prototypes, i.e., B. bifidum PRL2010, B. breve PRL2012, and B. longum PRL2022 were cultivated individually as well as in bi- and tri-association in a human gut-simulating medium. Transcriptomic analyses of these co-associations revealed up-regulation of genes predicted to be involved in the production of extracellular structures including pili (i.e., flp pilus assembly TadE protein gene), exopolysaccharides (i.e., GtrA family protein gene) and teichoic acids (i.e., ABC transporter permease), along with carbohydrate, amino acid and vitamin metabolism-related genes (i.e., exo-alpha-sialidase; beta-galactosidase and pyridoxamine kinase), suggesting that co-cultivation of bifidobacteria induces a response, in individual bifidobacterial strains, aimed at enhancing their proliferation and survival, as well as their ability to cooperate with their host to promote their persistence. Furthermore, exposure of the selected prototypes to human cell line monolayers unveiled the ability of the bifidobacterial tri-association to communicate with their host by increasing the expression of genes involved in adherence to/interaction with intestinal human cells. Lastly, bifidobacterial tri-association promoted the transcriptional upregulation of genes responsible for maintaining the integrity and homeostasis of the intestinal epithelial barrier.

Strain-specific effect of Streptococcus thermophilus consumption on host physiology

Streptococcus thermophilus is one of the most prevalent species in stool samples of westernized populations due to continuous exposure to fermented dairy products. However, few studies have explored the effect on host physiology by multiple S. thermophilus strains and considered the inter-strain differences in regulating host. In the present study, we investigated how four S. thermophilus strains influenced the gut microbiota, mucin changes, and host metabolism after 28 days of intervention in conventional mice. The results indicated that the consumption of S. thermophilus affected the host with strain specificity. Among four S. thermophilus strains, DYNDL13-4 and DQHXNQ38M61, especially DQHXNQ38M61, had more effect on host physiology by modulating gut microbiota and host metabolism than LMD9 and 4M6. Ingestion of strains DYNDL13-4 and DQHXNQ38M61 resulted in more remarkable changes in amino acid metabolism and lipid metabolism than that of strains LMD9 and 4M6, which may be related to the elevation of intestinal Bifidobacterium by DYNDL13-4 and DQHXNQ38M61. The enriched Coriobacteriaceae UCG-002, Rikenellaceae RC9 gut group, and Lactobacillus only in the DQHXNQ38M61 group, had a close relationship with the prominent effect of DQHXNQ38M61 on regulating amino acid and lipid metabolism. In addition, DQHXNQ38M61 had a strong influence on degrading colonic mucin fucose by decreased α-fucosidase activity in feces, and improving mucin sulfation by upregulated Gal3ST2 expression. Comparative genomic analysis revealed that the four S. thermophilus strains belonged to different branches in the phylogenetic tree, and DYNDL13-4 and DQHXNQ38M61 had more genes involved in carbohydrate metabolism, amino acid metabolism, membrane transport, and signal transduction, which may confer the capacity of nutrient utilization and gastrointestinal adaptation of the strains and be associated with their strong regulation in host. Our study provides valuable information for understanding the regulation of host metabolism after consuming different S. thermophilus strains and could facilitate potential personalized applications of S. thermophilus based on strain varieties.

Diversity Analysis of Intestinal Bifidobacteria in the Hohhot Population.

(1) Background: Bifidobacterium plays a pivotal role within the gut microbiota, significantly affecting host health through its abundance and composition in the intestine. Factors such as age, gender, and living environment exert considerable influence on the gut microbiota, yet scant attention has been directed towards understanding the specific effects of these factors on the Bifidobacterium population. Therefore, this study focused on 98 adult fecal samples to conduct absolute and relative quantitative analyses of bifidobacteria. (2) Methods: Using droplet digital PCR and the PacBio Sequel II sequencing platform, this study sought to determine the influence of various factors, including living environment, age, and BMI, on the absolute content and biodiversity of intestinal bifidobacteria. (3) Results: Quantitative results indicated that the bifidobacteria content in the intestinal tract ranged from 106 to 109 CFU/g. Notably, the number of bifidobacteria in the intestinal tract of the school population surpassed that of the off-campus population significantly (p = 0.003). Additionally, the group of young people exhibited a significantly higher count of bifidobacteria than the middle-aged and elderly groups (p = 0.041). The normal-weight group displayed a significantly higher bifidobacteria count than the obese group (p = 0.027). Further analysis of the relative abundance of bifidobacteria under different influencing factors revealed that the living environment emerged as the primary factor affecting the intestinal bifidobacteria structure (p = 0.046, R2 = 2.411). Moreover, the diversity of bifidobacteria in the intestinal tract of college students surpassed that in the out-of-school population (p = 0.034). This was characterized by a notable increase in 11 strains, including B. longum, B. bifidum, and B. pseudolongum, in the intestinal tract of college students, forming a more intricate intestinal bifidobacteria interaction network. (4) Conclusions: In summary, this study elucidated the principal factors affecting intestinal bifidobacteria and delineated their characteristics of intestinal bifidobacteria in diverse populations. By enriching the theory surrounding gut microbiota and health, this study provides essential data support for further investigations into the intricate dynamics of the gut microbiota.

Lactic Acid Bacteria-Fermented Diet Containing Bacterial Extracellular Vesicles Inhibited Pathogenic Bacteria in Striped Beakfish (Oplegnathus fasciatus)

In recent years, probiotics have received considerable attention for improving the health of aquaculture organisms, such as fish and shrimp, by stimulating immune activity and increasing growth rates. Oplegnathus fasciatus is a common and economically important cultured fish species in Asia. In this study, we aimed to investigate the potential of lactic acid bacteria (LAB; Limosilactobacillus reuteri)-fermented feed to promote growth and enhance immune function in O. fasciatus. The feed contained the highest proportion of LAB after L. reuteri fermentation for 3 days in anaerobic conditions. Oplegnathus fasciatus was fed LAB-fermented feed for 30 days. The administration of LAB-fermented feed (live bacteria > 109 CFU/g) significantly increased the growth rate (weight gain = 174.8%; FCR = 4.23) and intestinal probiotic levels of O. fasciatus. After LAB-fermented feeding, the immunity index was evaluated by superoxide anion production, the phagocytic activity of leukocytes, and bactericidal and lysozyme activities in the serum of O. fasciatus. We found that LAB-fermented feed treatment potentially elevated the proportions of intestinal Bifidobacterium, Blautia, and Dorea species and reduced pathogenic bacterial growth (Acinetobacter, Escherichia_Shigella, and Megasphaera) in O. fasciatus. This study demonstrated that LAB-fermented feed containing extracellular vesicles improves growth performance and the inhibition of pathogenic Acinetobacter baumannii.

Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.

Effect of Continuous Ingestion of Bifidobacteria and Dietary Fiber on Improvement in Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Trial.

Bifidobacterium animalis subsp. lactis GCL2505 has been shown to have some positive effects on health, including improved defecation frequency and reduced visceral fat. These effects are thought to be due to GCL2505's unique ability to reach the intestine in a viable form and proliferate after a single intake. This leads to an increased number of intestinal bifidobacteria. This randomized, double-blind, placebo-controlled, parallel-group study was conducted to confirm that intake of GCL2505 and inulin (a prebiotic) improve cognitive function (n = 80). Participants consumed test drinks containing 1 × 1010 colony-forming units of GCL2505 per 100 g and 2.0 g of inulin per 100 g for 12 weeks. The change in cognitive function assessment scores was set as the primary endpoint. There were significant improvements in scores in the neurocognitive index domain, which is an assessment of overall cognitive function, in addition to overall attention, cognitive flexibility, and executive function domains. The intervention significantly increased the number of fecal bifidobacteria and affected the levels of several inflammatory markers. These results suggest that intake of GCL2505 and inulin improves cognitive function by improving the intestinal environment and alleviating inflammation.

Changes of Intestinal Flora and the Effect on Intestinal Function in Infants With Ventricular Septal Defect After Cardiopulmonary Bypass Surgery

This study aimed to investigate the changes in intestinal flora in infants with ventricular septal defect (VSD) after cardiopulmonary bypass (CPB) surgery and their potential relationship with postoperative gastrointestinal function recovery. Fecal samples of 20 infants with VSD were collected before and after CPB surgery at our hospital from September 2021 to March 2022. 16S rRNA was used to detect and analyze the fecal samples. The most abundant intestinal microbes in the preoperative intestinal flora were Enterococcus (37.14%), Bifidobacterium (20.71%), Shigella (8.15%), Streptococcus (5.19%), Lactobacillus (3.7%), Rothia (2.22%). However, the most abundant intestinal microbes in the postoperative intestinal flora were Enterococcus (49.63%), Bifidobacterium (12.59%), Shigella (10.37%), Streptococcus (8.14%), Rothia (4.43%). The diversity and species richness of intestinal flora after CPB surgery were significantly lower than those preoperatively. The intestinal Enterococcus content in patients with postoperative gastrointestinal dysfunction was significantly higher than that in patients without gastrointestinal dysfunction (P < 0.05). Intestinal Bifidobacterium content in patients with postoperative gastrointestinal dysfunction was significantly lower than that in patients without gastrointestinal dysfunction (P < 0.05). After surgery, the content of intestinal Enterococcus was negatively correlated with the full feeding time, and the content of intestinal Bifidobacterium was positively correlated with full feeding time. After CPB surgery, the diversity and richness of intestinal flora decreased, intestinal pathogenic bacteria increased, and beneficial intestinal bacteria decreased. An increase in Enterococcus and decrease in Bifidobacterium can increase the incidence of gastrointestinal dysfunction and prolong the recovery time of gastrointestinal function.

Bacillus subtilis KC1 prevents Mycoplasma gallisepticum-induced lung injury by enhancing intestinal Bifidobacterium animalis and regulating indole metabolism in chickens

It has been reported that dietary administration of Bacillus subtilis KC1 is effective in alleviating lung injury induced by Mycoplasma gallisepticum (MG) infection in chickens. However, the underlying molecular mechanism of B. subtilis KC1 against MG infection is still unclear. The purpose of this study was to determine whether B. subtilis KC1 could alleviate MG infection-induced lung injury in chickens by regulating their gut microbiota. The results of this study indicate that B. subtilis KC1 supplementation has the potential to alleviate MG infection-induced lung injury as reflected by reduced MG colonization, reduced pathologic changes, and decreased production of pro-inflammatory cytokines. In addition, B. subtilis KC1 supplementation was partially effective in alleviating the gut microbiota disorder caused by MG infection. Importantly, B. subtilis KC1 enriched the beneficial Bifidobacterium animalis in gut and thus reversed indole metabolic dysfunction caused by MG infection. B. subtilis KC1 supplementation increased levels of indole, which enhanced aryl hydrocarbon receptor activation, improving barrier function and alleviating lung inflammation caused by MG. Overall, this study indicates that B. subtilis KC1 has a "gut-lung axis" mechanism that can reduce the severity of MG infection by enriching intestinal B. animalis and regulating indole metabolism.

Screening of Bifidobacteria with Probiotic Potential from Healthy Infant Feces by Using 2'-Fucosyllactose.

Using 2'-fucosyllactose (2'-FL) as the sole carbon source can be an efficient way to screen bifidobacteria with superior probiotic capabilities since 2'-FL is a key element in promoting the growth of intestinal bifidobacteria in newborns. This approach was used in this work to screen eight bifidobacteria strains, including one strain of Bifidobacterium longum subsp. infantis BI_Y46 and seven strains of Bifidobacterium bifidum (BB_Y10, BB_Y30, BB_Y39, BB_S40, BB_H4, BB_H5 and BB_H22). Studies on their probiotic properties showed that BI_Y46 had a unique morphology with pilus-like structure, a high resistance to bile salt stimulation and a potent inhibitory action on Escherichia coli ATCC 25922. Similarly, BB_H5 and BB_H22 produced more extracellular polysaccharides and had a higher protein content than other strains. In contrast, BB_Y22 displayed considerable auto-aggregation activity and a high resistance to bile salt stimulation. Interestingly, BB_Y39 with weak self-aggregation ability and acid resistance had very excellent bile salt tolerance, extracellular polysaccharides (EPS) production and bacteriostatic ability. In conclusion, 2'-FL was used as sole carbon source to identify eight bifidobacteria with excellent probiotic properties.

Dynamic changes of the gut microbial colonization in preterm infants with different time points after birth.

Risks associated with preterm birth are unevenly distributed across all gestations. At earlier gestational ages, complications such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) conditions are significantly more common and are associated with a shift in the composition of the gut microbiome. Conventional bacterial culture techniques demonstrate that the colonization of the gut microbiota of preterm infants differs significantly from that of healthy-term infants. The current study aimed to investigate the impact of preterm infancy on the dynamic changes of fecal microbiota in preterm infants at different time points (1, 7, 14, 21, 28, and 42 days) after birth. We selected 12 preterm infants hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2017 to December 2017. A total of 130 fecal specimens from preterm infants were analyzed using 16S rRNA gene sequencing. We found that the colonization process of fecal microbiota in preterm infants is highly dynamic at different time points after birth, i.e., Exiguobacterium, Acinetobacter, and Citrobacter showed a declining abundance pattern with the advancement of age, while the bacterial groups of Enterococcus (Klebsiella and Escherichia coli) gradually grew and became the main microbiota during the development of fecal microbiota in preterm infants at the age of 42 days. Furthermore, the colonization of intestinal Bifidobacteria in preterm infants was relatively late and did not rapidly become the predominant microbiota. Moreover, the results also showed the presence of Chryseobacterium bacterial group, whose colonization was different in different time point groups. Conclusively, our findings deepen our comprehension and offer new perspectives on targeting particular bacteria in the treatment of preterm infants at different time points after birth.

Combination of poly-γ-glutamic acid and galactooligosaccharide improves intestinal microbiota, defecation status, and relaxed mood in humans: a randomized, double-blind, parallel-group comparison trial.

The genus Bifidobacterium comprises beneficial intestinal bacteria that play a crucial role in the regulation of human health. Traditional prebiotics are known to increase intestinal bifidobacteria by supplying a carbon source necessary for their growth. However, intestinal bifidobacteria need not only a carbon source but also a nitrogen source for growth. Moreover, the growth of bifidobacteria is known to be inhibited in a culture medium that does not contain glutamic acid. Based on these reports, we hypothesized that the combined intake of traditional prebiotics and glutamic acid would be beneficial for growth of bifidobacteria in the gut. In this study, we investigated the effects of the combination of galactooligosaccharide (GOS; traditional prebiotic material) and poly-γ-glutamic acid (γ-PGA; source of glutamic acid) and only GOS on the intestinal microbiota and health conditions (including intestinal regulation, mood status, gastrointestinal condition, skin condition, and sleep quality) in a randomized, double-blind, parallel-group comparison trial in healthy subjects. The combined intake of GOS and γ-PGA significantly increased the prevalence of B. longum compared to the intake of GOS alone. A minimum effective dose of 2.0 g GOS and 0.3 g γ-PGA improved defecation and mood status. We revealed the combined effects of GOS and γ-PGA on intestinal microbiota as well as physical condition and concluded that the delivery of glutamic acid to the large intestine with traditional prebiotics is useful as an advanced prebiotic.

Human Milk Oligosaccharide Utilization in Intestinal Bifidobacteria Is Governed by Global Transcriptional Regulator NagR.

ABSTRACTBifidobacterium longum subsp. infantis is a prevalent beneficial bacterium that colonizes the human neonatal gut and is uniquely adapted to efficiently use human milk oligosaccharides (HMOs) as a carbon and energy source. Multiple studies have focused on characterizing the elements of HMO utilization machinery in B. longum subsp. infantis; however, the regulatory mechanisms governing the expression of these catabolic pathways remain poorly understood. A bioinformatic regulon reconstruction approach used in this study implicated NagR, a transcription factor from the ROK family, as a negative global regulator of gene clusters encoding lacto-N-biose/galacto-N-biose (LNB/GNB), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT) utilization pathways in B. longum subsp. infantis. This conjecture was corroborated by transcriptome profiling upon nagR genetic inactivation and experimental assessment of binding of recombinant NagR to predicted DNA operators. The latter approach also implicated N-acetylglucosamine (GlcNAc), a universal intermediate of LNT and LNnT catabolism, and its phosphorylated derivatives as plausible NagR transcriptional effectors. Reconstruction of NagR regulons in various Bifidobacterium lineages revealed multiple potential regulon expansion events, suggesting evolution from a local regulator of GlcNAc catabolism in ancestral bifidobacteria to a global regulator controlling the utilization of mixtures of GlcNAc-containing host glycans in B. longum subsp. infantis and Bifidobacterium bifidum.IMPORTANCE The predominance of bifidobacteria in the gut of breastfed infants is attributed to the ability of these bacteria to metabolize human milk oligosaccharides (HMOs). Thus, individual HMOs such as lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are considered promising prebiotics that would stimulate the growth of bifidobacteria and confer multiple health benefits to preterm and malnourished children suffering from impaired (stunted) gut microbiota development. However, the rational selection of HMO-based prebiotics is hampered by the incomplete knowledge of regulatory mechanisms governing HMO utilization in target bifidobacteria. This study describes NagR-mediated transcriptional regulation of LNT and LNnT utilization in Bifidobacterium longum subsp. infantis. The elucidated regulatory network appears optimally adapted to simultaneous utilization of multiple HMOs, providing a rationale to add HMO mixtures (rather than individual components) to infant formulas. The study also provides insights into the evolutionary trajectories of complex regulatory networks controlling carbohydrate metabolism in bifidobacteria.

Effect and Mechanism of Flavored Tongxie Yaofang Decoction for Diarrheal Irritable Bowel Syndrome under Intestinal Microecology.

This research was to analyze the effect of flavored Tongxie Yaofang on diarrheal irritable bowel syndrome (IBS) by the situation of intestinal microecology. The treatment mechanism was analyzed, so as to provide a more effective treatment method for patients clinically. 60 IBS patients were selected as the research objects and were divided according to the different treatment methods. For the control group (n = 20 cases), oral pinaverium bromide tablets were given. For the treatment group (n = 40 cases), the flavored Tongxie Yaofang decoction was given in addition to conventional treatment. The curative effects on the two groups of patients were evaluated in combination with the changes in intestinal microecology. With the syndrome score, the total effective rate of the treatment group (92.5%) was obviously superior to the control group (80%) (P < 0.05). The clinical symptoms such as abdominal pain, abdominal distension, and diarrhea in the treatment group were significantly relieved after treatment in contrast to the control group (P < 0.05). Intestinal Bifidobacterium, Escherichia coli, and Bifidobacterium/Escherichia coli (B/E) ratio were all greatly higher than those in the control group (P < 0.05). In summary, flavored Tongxie Yaofang had a good effect in improving the symptoms of patients with diarrheal IBS and improved the microflora of Bifidobacterium and Escherichia coli in the intestinal tract of patients.

Clostridium butyricum powders combined with zinc gluconate on inflammatory factors and intestinal microecology in children with infectious diarrhea

Objective: To investigate the clinical value of Clostridium butyricum powders combined with zinc gluconate in the treatment of infectious diarrhea in children, clinical data of 86 children with infectious diarrhea were retrospectively analyzed. Methods: Both groups received routine treatments to reduce symptoms, among which the control group ( n = 40) was given Clostridium butyricum powders, and the experiment group ( n = 46) was given Clostridium butyricum powders and zinc gluconate. Patients in both groups were treated for 5 days. The clinical efficacy, recovery time, safety, serum levels of inflammatory markers (interleukin-6, interleukin-17, C-reactive protein), indicators of the intestinal mucosal function (diamine oxidase, D-lactate) and indicators to intestinal microecology (bifidobacteria, lactobacillus) before and after treatment were compared between the two groups. Results: The clinical efficacy in the experiment group (95.65%) was higher than that in the control group (77.50%, p &lt; 0.05). The time of recovery from symptoms including diarrhea, abdominal pain and vomiting, and to normal body temperature in the experiment group were shorter than those in the control group (all p &lt; .001). After treatment, the serum IL-6, IL-17, CRP levels and DAO, D-lactate levels in both groups were lower than those before treatment, and were lower in the experiment group than in the control group (all p &lt; .001). After treatment, the intestinal bifidobacteria and lactobacillus levels in both groups were higher than those before treatment, and were higher in the experiment group than in the control group (all p &lt; .01). There was no significant difference in the incidence of adverse reactions between the experiment group (8.70%) and the control group (2.50%). Conclusion: In this open-label study, Clostridium butyricum powders combined with zinc gluconate are significantly effective in treating children with infectious diarrhea, which is conducive to relieving early symptoms, downregulating serum inflammatory factor levels, improving intestinal mucosal function, regulating intestinal microecology, and ensuring the safety of patients.

Cure of the intestinal disorders

The volunteer with chronic pancreatitis has been cured from the lipase absence in his duodenal content during the food intake. The human intestinal bifidobacterium has been genetically modified to express recombinant human pancreatic lipase absent. The described study again confirms the human intestine for the delivery of the recombinant proteins, including the delivery to the blood circulation. This is the naturally occurring gate for the recombinant proteins, opening new frontiers in the recombinant vaccines delivery for less then 200 hours and the recombinant proteins delivery instead of the scientifically compromised adenoviral delivery system used by the genetic engineering companies around the World. Key Words: pancreatic lipase insufficiency; new gates for recombinant proteins delivery.

Lactitol Supplementation Modulates Intestinal Microbiome in Liver Cirrhotic Patients.

Background: Cirrhosis is a common chronic liver disease characterized by irreversible diffuse liver damage. Intestinal microbiome dysbiosis and metabolite dysfunction contribute to the development of cirrhosis. Lactitol (4-β-D-galactopyranosyl-D-glucitol) was previously reported to promote the growth of intestinal Bifidobacteria. However, the effect of lactitol on the intestinal microbiome and fecal short-chain fatty acids (SCFAs) and bile acids (BAs) and the interactions among these factors in cirrhotic patients pre- and post-lactitol treatment remain poorly understood.Methods: Here, using shotgun metagenomics and targeted metabolomics methods.Results: we found that health-promoting lactic acid bacteria, including Bifidobacterium longum, B.pseudocatenulatum, and Lactobacillus salivarius, were increased after lactitol intervention, and significant decrease of pathogen Klebsiella pneumonia and associated antibiotic resistant genes /virulence factors. Functionally, pathways including Pseudomonas aeruginosa biofilm formation, endotoxin biosynthesis, and horizontal transfer of pathogenic genes were decreased in cirrhotic patients after 4-week lactitol intervention compared with before treatment.Conclusion: We identified lactitol-associated metagenomic changes, and provide insight into the understanding of the roles of lactitol in modulating gut microbiome in cirrhotic patients.

Effect of warm-needle moxibustion intervention on immune function and intestinal flora in patients after colorectal cancer radical operation

To explore the effect of warm-needle moxibustion (WNM) on the levels of T cell subgroups and serum inflammatory factors, intestinal microecological balance and postoperative adverse reactions in patients with colorectal cancer. Eighty-four patients who underwent elective radical resection of colorectal cancer were randomly and equally divided into control (medication) group (23 men and 19 women) and WNM group (24 men and 18 women). Patients of the control group received conventional medication treatment (such as postoperative anti-infection and fluid supplementation), and those of the WNM group received conventional medication plus WNM stimulation (the acupuncture needle handle warmed by ignited moxa stick) of bilateral Zusanli(ST36), Sanyinjiao(SP6), Yinlingquan(SP9), Shangjuxu(ST37), and Zhaohai(KI6). The acupuncture needles were retained for 45 minutes every time, starting on the first day after surgery, once a day for 15 days. The number of T cell subsets (CD3+, CD4+, CD8+) positive cells was counted under fluorescence microscope, and the contents of serum tumor necrosis factor α(TNF-α) and interleukin-6 (IL-6) were detected by using ELISA, and the level of C-reactive protein (CRP) was detected by using immunoturbidimetry. The levels (logarithm of colony-forming units per gram of wet fecal weight) of Bifidobacterium, Lactobacillus, Escherichia coli and Enterococcus were determined. The adverse reactions (leukocyte decline, nausea and vomiting, peripheral phlebitis, cold stimulation sensitivity) were recorded after surgery. Before treatment, there were no significant differences between the two groups in the number of T cell subgroups, TNF-α and IL-6 contents, and intestinal flora numbers (P>0.05). After the treatment, self-comparison showed that the numbers of CD3+ and CD4+ positive cells, the ratio of CD4+/CD8+ and the intestinal Bifidobacterium and Lactobacillus levels in the WNM group were significantly increased (P<0.05), whereas the number of CD8+positive cells, intestinal Escherichia coli and Enterococcus levels in the WNM group, and the levels of TNF-α, IL-6 and CRP in both groups were obviously decreased in comparison with their own pretreatment (P<0.05), but no significant changes were found in the levels of CD3+ and CD4+ positive cells, CD4+/CD8+ and intestinal Bifidobacterium, Lactobacillus, Escherichia coli and Enterococcus in the control group (P>0.05). Comparison between two groups displayed that after the treatment, the numbers of CD3+ and CD4+ positive cells, the ratio of CD4+/CD8+, as well as the levels of Bifidobacterium and Lactobacillus were significantly higher in the WNM group than in the control group (P<0.05), whereas the number of CD8+ positive cells， TNF-a, IL-6 and CRP, and the levels of Escherichia coli and Enterococcus were obviously lower in the WNM group than in the control group (P<0.05). The incidence of adverse reactions including leukopenia, nausea and vomiting, peripheral phlebitis, and sensitivity to cold stimulation in the WNM group were markedly lower than those of the control group (P<0.05). WNM intervention can significantly improve the immune function, reduce the level of inflammatory factors, regulate the level of beneficial intestinal flora, and also reduce the incidence of postoperative adverse reactions in patients experiencing radical resection of colorectal cancer.

Tannins extract from Galla Chinensis can protect mice from infection by Enterotoxigenic Escherichia coli O101

BackgroundEnterotoxigenic Escherichia coli (ETEC) is classically associated with acute secretory diarrhea, which induces 2 million people death in developing countries over a year, predominantly children in the first years of life. Previously, tannins (47.75%) were extracted from Galla Chinensis and prepared as Galla Chinensis oral solution (GOS) which showed significant antidiarrheal activity in a castor oil-induced diarrhea in mice. Whether the tannins extract were also effective in treatment of ETEC-induced diarrhea was determined in this study.MethodsMice were randomly divided into 6 groups (n = 22). The mice in the normal and untreated groups were given normal saline. Three GOS-treated groups were received different concentrations of GOS (5, 10 and 15%, respectively) at a dose of 10 mL/kg. Mice in the positive control group were fed with loperamide (10 mg/kg). The treatment with GOS started 3 days before infection with ETEC and continued for 4 consecutive days after infection. On day 3, mice were all infected with one dose of LD50 of ETEC, except those in the normal group. Survival of mice was observed daily and recorded throughout the study. On days 4 and 7, samples were collected from 6 mice in each group.ResultsGOS could increase the survival rate up to 75%, while in the untreated group it is 43.75%. The body weights of mice treated with 15% GOS were significantly increased on day 7 in comparison with the untreated group and the normal group. GOS-treatment recovered the small intestine coefficient enhanced by ETEC-infection. The diarrhea index of mice treated with GOS was significantly decreased. GOS increased the levels of IgG and sIgA in the terminal ileum and decreased the levels of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1β, IL-6 and IL-8) in serum. GOS could increase the amount of intestinal probiotics, Lactobacilli and Bifidobacteria. GOS could alleviate colon lesions induced by ETEC-infection. GOS showed higher potency than loperamide.ConclusionsGOS could be a promising drug candidate for treating ETEC infections.

Impact of synbiotics on gut microbiota during early life: a randomized, double-blind study

Human milk is considered the optimal nutrition for infants and found to contain significant numbers of viable bacteria. The aim of the study was to assess the effects of a specific synbiotic combination at doses closer to the bacterial cells present in human milk, on intestinal bifidobacteria proportions (relative abundance), reduction of potential pathogens and gut physiological conditions. A clinical study was conducted in 290 healthy infants aged from 6 to 19 weeks. Infants received either a control infant formula or one of the two investigational infant formulas (control formula with 0.8 g/100 ml scGOS/lcFOS and Bifidobacterium breve M-16V at either 1 × 104 cfu/ml or 1 × 106 cfu/ml). Exclusively breastfed infants were included as a reference. Analyses were performed on intention-to-treat groups and all-subjects-treated groups. After 6 weeks of intervention, the synbiotics at two different doses significantly increased the bifidobacteria proportions in healthy infants. The synbiotic supplementation also decreased the prevalence (infants with detectable levels) and the abundance of C. difficile. Closer to the levels in the breastfed reference group, fecal pH was significantly lower while l-lactate concentrations and acetate proportions were significantly higher in the synbiotic groups. All formulas were well tolerated and all groups showed a comparable safety profile based on the number and severity of adverse events and growth. In healthy infants, supplementation of infant-type bifidobacterial strain B. breve M-16V, at a dose close to bacterial numbers found in human milk, with scGOS/lcFOS (9:1) created a gut environment closer to the breastfed reference group. This specific synbiotic mixture may also support gut microbiota resilience during early life.Clinical Trial Registration This clinical study named Color Synbiotics Study, was registered in ClinicalTrials.gov on 18 March 2013. Registration number is NCT01813175. https://clinicaltrials.gov/ct2/show/NCT01813175.

Lactulose ingestion causes an increase in the abundance of gut-resident bifidobacteria in Japanese women: a randomised, double-blind, placebo-controlled crossover trial.

The genus Bifidobacterium comprises various bacterial species, and the complement of species within the human intestinal tract differs from individual to individual. The balance of these bifidobacterial species remains poorly understood, although it is known that the abundance of bifidobacteria increases following the ingestion of prebiotics. We previously conducted a randomised, placebo-controlled, double-blind, crossover study of 2 g/day lactulose ingestion for 2 weeks in 60 Japanese women. To study the effect of lactulose ingestion on each bifidobacterial species, here, we measured the abundance of each of the principal bifidobacterial species. After lactulose ingestion, the log cell counts of the Bifidobacterium adolescentis group (8.97±0.08 vs 9.39±0.08, P=0.0019), Bifidobacterium catenulatum group (9.45±0.10 vs 9.65±0.10, P=0.0032) and Bifidobacterium longum group (9.01±0.07 vs 9.29±0.07, P=0.0012) were significantly higher than in the placebo ingestion control group. However, the log cell counts were similar for Bifidobacterium breve (8.12±0.12 vs 8.33±0.12, P=0.20), Bifidobacterium bifidum (9.08±0.12 vs 9.42±0.14, P=0.095) and Bifidobacterium animalis subspecies lactis (8.65±0.53 vs 8.46±0.46, P=0.77). Cluster analysis of the log cell count data at the bifidobacterial species level revealed three distinct clusters, but the combinations and ratios of the constituent bifidobacteria were not affected by lactulose ingestion. Furthermore, principal coordinate analysis of the intestinal microbiota in the lactulose and placebo ingestion groups using Illumina MiSeq showed no significant differences in the intestinal microbiota as a whole. These results suggest that 2 g/day lactulose ingestion for 2 weeks significantly increases the abundance of intestinal bifidobacteria, but does not affect the intestinal microbiota as a whole.