Anti-cancer Activity of Human Gastrointestinal Bacteria

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

Rosmarinic Acid and Sodium Citrate Have a Synergistic Bacteriostatic Effect against Vibrio Species by Inhibiting Iron Uptake

Background: New strategies are needed to combat multidrug-resistant bacteria. The restriction of iron uptake by bacteria is a promising way to inhibit their growth. We aimed to suppress the growth of Vibrio bacterial species by inhibiting their ferric ion-binding protein (FbpA) using food components. Methods: Twenty spices were selected for the screening of FbpA inhibitors. The candidate was applied to antibacterial tests, and the mechanism was further studied. Results: An active compound, rosmarinic acid (RA), was screened out. RA binds competitively and more tightly than Fe3+ to VmFbpA, the FbpA from V. metschnikovii, with apparent KD values of 8 μM vs. 17 μM. Moreover, RA can inhibit the growth of V. metschnikovii to one-third of the control at 1000 μM. Interestingly, sodium citrate (SC) enhances the growth inhibition effect of RA, although SC only does not inhibit the growth. The combination of RA/SC completely inhibits the growth of not only V. metschnikovii at 100/100 μM but also the vibriosis-causative pathogens V. vulnificus and V. parahaemolyticus, at 100/100 and 1000/100 μM, respectively. However, RA/SC does not affect the growth of Escherichia coli. Conclusions: RA/SC is a potential bacteriostatic agent against Vibrio species while causing little damage to indigenous gastrointestinal bacteria.

Increased levels of circulating LPS during Tuberculosis prevails in patients with advanced pulmonary involvement

Our earlier studies in tuberculosis (TB) patients indicate that in those where the process evolves to a larger pulmonary involvement, the immune endocrine response may promote an unfavorable environment. Chronic infectious diseases, and their persistent proinflammatory response, may affect mucosal barriers integrity favoring the translocation of gastrointestinal bacteria, leading to an increase of circulating lipopolysaccharides (LPS). Consequently, we quantified LPS levels in TB patients, with different degrees of pulmonary involvement, and controls (Co) and analyzed the possible relationship between LPS and inflammatory mediators i.e., C reactive protein (CRP), interleukin 6 (IL-6) and Interferon-gamma (IFN-γ), Erythrocyte Sedimentation Rate (ESR), steroid hormones (Cortisol and Dehydroepiandrosterone, DHEA), and inflammatory transcripts from peripheral blood mononuclear cells (IL-1β, IL-6, IFN-γ). LPS was assessed by the Limulus amoebocyte lysate assay and the ELISA technique was used to quantify hormones and cytokines in the plasma samples. Cytokine transcripts from PBMC were evaluated by qRT-PCR. Non-parametric tests were used. LPS levels were increased in TB patients, as did levels of CRP, IL-6, IFN-γ, cortisol and ESR. Severe patients had the highest amounts of circulating LPS; with moderate and severe cases showing much higher levels of CRP, ESR, IL-6, IFN-γ and cortisol/DHEA ratio, as an endocrine imbalance. Only in PBMC from severe cases was mRNA for IL-1β increased. Correlation analysis showed that levels of LPS from severe patients were positively associated with IL-6 and IFN-γ plasma concentrations and with IL-1β transcripts, while IL-6 had a positive correlation with the cortisol/DHEA ratio. The higher levels of circulating LPS during progressive TB may emerge as a contributing factor for the persistence of the greater immune endocrine imbalance distinctive of advanced disease, which might suggest a vicious cycle among LPS, inflammation and endocrine imbalance.

Growth performances, gastrointestinal epithelium and bacteria responses of Yellow-feathered chickens to kudzu-leaf flavonoids supplement

The objective of this study was to investigate the effects of replacing antibiotics with Kudzu-leaf flavonoids (KLF) on the growth performances, gut epithelial development, and gastrointestinal bacteria diversities of Yellow-feathered broilers. For this purpose, total of 216 1-day-old male Yellow-feathered chickens with the similar birth weight (31.0 ± 1.0 g) were randomly divided into 3 treatments: the control treatment (CON), the kudzu-leaf flavonoids supplement treatment (KLF), and the antibiotics supplement treatment (AGP). All birds were provided with a 56 d-feeding procedure, followed by the measurement of production performances, immune organs, blood anti-oxidant parameters, intestine epithelium development, and cecal microbiota. Results showed the feed conversion ratio significantly decreased after KLF supplement compared with CON (P < 0.05). KLF supplement partly promoted the anti-oxidant capacity on account of the increased activity of Superoxide dismutase (SOD) and the decrease content of malondialdehyde (MDA). Further, as referred to the gastrointestinal development and bacteria, ratio of villus/crypt significantly increased of ileum in KLF treatment (P < 0.05) while a significant promition of bacterial diversity and partial representative probiotic bacteria (P < 0.05) after KLF supplementation. Moreover, correlation analysis indicated that probitics including Bifidobacterium, Butyricimonas, Lactobacillus and Streptococcus positively correlated with production performances. In conclusion, KLF supplement may promote feed efficiency and benefit the gastrointestinal health through improving gut bacterial diversity and probiotic bacteria. The KLF might be applied as a proper antibiotic alternative.

Evaluation of the Fecal Bacterial Communities of Angus Steers With Divergent Feed Efficiencies Across the Lifespan From Weaning to Slaughter

Numerous studies have examined the link between the presence of specific gastrointestinal bacteria and the feed efficiency of cattle. However, cattle undergo dietary changes during their productive life which can cause fluctuations in their microbial consortium. The objective of the present study was to assess changes in the fecal microbiome of beef steers genetically selected to be divergent in feedlot feed efficiency, to determine whether differences in their fecal microbiomes could be detected as early as weaning, and continued throughout the rearing process regardless of dietary changes. Fecal samples were collected at weaning, yearling age, and slaughter for a group of 63 steers. Based on their feedlot-finishing performance, the steers were selected and divided into two groups according to their residual feed intake (RFI): efficient steers (low-RFI; n = 7) and inefficient steers (high-RFI; n = 8). To ascertain the fecal microbial consortium and volatile fatty acid (VFA) content, 16S rRNA gene sequencing and VFA analysis were performed. Overall, bacterial evenness and diversity were greater at weaning compared to yearling and slaughter for both efficiency groups (P &lt; 0.001). Feedlot RFI linearly decreased as both Shannon diversity and Ruminococcaceae abundance increased (R2 = 65.6 and 60.7%, respectively). Abundances of Ruminococcaceae, Rikenellaceae, and Christensenellaceae were higher at weaning vs. yearling age and slaughter (P &lt; 0.001); moreover, these families were consistently more abundant in the feces of the low-RFI steers (for most of the timepoints evaluated; P ≤ 0.05), compared to the high-RFI steers. Conversely, abundances of Bifidobacteriaceae were numerically higher in the feces of the high-RFI steers throughout their lifespan. Total VFA concentrations increased at slaughter compared to weaning and yearling for both efficiency groups (P &lt; 0.001). The acetate:propionate ratio decreased linearly (P &lt; 0.001) throughout the life of the steers regardless of their efficiency, reflective of dietary changes. Our results indicate that despite fluctuations due to animal age and dietary changes, specific bacterial families may be correlated with feed efficiency of steers. Furthermore, such differences may be identifiable at earlier stages of the production cycle, potentially as early as weaning.

Biliary Microbial Structure of Gallstone Patients With a History of Endoscopic Sphincterotomy Surgery

The biliary microbiota is related to the pathogenesis of human bile duct stones. However, the extent to which a history of invasive endoscopic sphincterotomy (EST) affects the biliary bacterial community remains largely unknown. We collected bile samples from the common bile duct of 100 choledocholithiasis patients. We performed 16S rRNA sequencing to investigate and compare the biliary microbial community. The patients without antibiotic treatment (AT) were grouped into three clusters based on their biliary microbial compositions. The patients with a history of EST were significantly enriched in one cluster mainly consisting of gastrointestinal bacteria compared with the other two clusters consisting of oral and environmental bacteria. The β-diversities of patients with and without EST were also significantly different, whereas the α-diversities were comparable. The only significantly enriched bacterial genus associated with a history of EST was Pyramidobacter, while eight other genera were significantly decreased. For patients with AT, seven of these genera maintained their association with EST, including Pyramidobacter. However, after AT, the difference in β-diversities was diminished. EST induced a marked shift in the biliary microbial composition. A cluster of biliary bacteria was associated with a history of EST, and Pyramidobacter was specific to EST.

Host Synthesized Carbohydrate Antigens on Viral Glycoproteins as “Achilles’ Heel” of Viruses Contributing to Anti-Viral Immune Protection

The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to α-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the α1,3galactosyltransferase gene 20–30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing α-gal epitopes, whereas few mutated offspring lacking α-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting α-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since α-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple α-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells.