Number Of Commensal Bacteria Research Articles

Research status and prospects of indoor airborne microbiome based on respiratory health effects

<p indent="0mm">Indoor environment is an important repository of microbiome. Environmental microbiome can influence immune protection through changing the commensal flora of the respiratory tract. The interaction between environment airborne microbiome and human microbiome contributes to human microbial diversity, provides immunomodulatory effects, and thus reduces the risk of respiratory diseases. Lack of immune modulation acquired through microbial exposure may lead to risk of chronic respiratory diseases. Clinical parameters, such as susceptibility, progression, and severity of respiratory disease, are associated with microbial changes. Chronic obstructive pulmonary disease, cystic fibrosis, asthma, and lung cancers are associated with airway microbial dysbiosis. The changes of microbiome during the disease period are mainly characterized by a decrease in overall bacterial diversity, a decrease in the number of commensal bacteria, and an increase in the number of potential pathogenic bacteria. Based on the perception that pathogenic or conditional pathogenic microbiome is responsible for the infection and transmission of respiratory and non-respiratory diseases, public health policies have long favored keeping indoors at lower concentrations of microbiome or even absolutely sterile. However, in the past decade, an in-depth understanding of the microbiology of the environment and human health has shifted researchers’ view of indoor microbiome from a purely pathogenic and infectious negative role to a potentially protective, preventive positive role. Facing with the dual health effects of indoor airborne microbiome, the ideal control strategy should be to increase the microbial diversity and the proportion of beneficial microbiome, while reducing the concentration of pathogenic microbiome for regions, seasons, and sensitive populations. However, there is still no paradigm shift in built environment microbiology due to technical bottlenecks that prevent researchers from establishing a causal relationship between indoor microbiome and health effects. Currently, the types and properties of indoor airborne microbiome are yet to be fully screened and understood. The characteristics of indoor microbiome when they exert health effects are yet to quantify, including microbial metabolization and reproduction in the respiratory tract, corresponding protective effects, and dose-response effects and individual variation in health effects. The answer to the question “What is a healthy indoor air microbial environment”, that is, the characterization of indoor airborne microbiome based on respiratory health effects, is hindered by respiratory microbial sampling, in-depth analysis of microbial data, and the accuracy of <italic>in vitro</italic> experiments. Subsequent research needs to focus on the development of the following techniques: Microbial sampling tools with low invasiveness, high efficiency and low cost; statistical tools with complex source identification, interference factor quantification and causal relationship judgment functions; and experimental tools capable of simulating real, complex respiratory environments and revealing molecular mechanisms of action <italic>in vivo</italic>. “What is a healthy indoor air microbial environment” will gradually become clear as these questions are resolved. A clear and quantitative mechanism will serve as a scientific basis to guide the improvement of indoor microbial control standards and the rational use of practical interventions.

Smallpox vaccination induces a substantial increase in commensal skin bacteria that promote pathology and influence the host response.

Interactions between pathogens, host microbiota and the immune system influence many physiological and pathological processes. In the 20th century, widespread dermal vaccination with vaccinia virus (VACV) led to the eradication of smallpox but how VACV interacts with the microbiota and whether this influences the efficacy of vaccination are largely unknown. Here we report that intradermal vaccination with VACV induces a large increase in the number of commensal bacteria in infected tissue, which enhance recruitment of inflammatory cells, promote tissue damage and influence the host response. Treatment of vaccinated specific-pathogen-free (SPF) mice with antibiotic, or infection of genetically-matched germ-free (GF) animals caused smaller lesions without alteration in virus titre. Tissue damage correlated with enhanced neutrophil and T cell infiltration and levels of pro-inflammatory tissue cytokines and chemokines. One month after vaccination, GF and both groups of SPF mice had equal numbers of VACV-specific CD8+ T cells and were protected from disease induced by VACV challenge, despite lower levels of VACV-neutralising antibodies observed in GF animals. Thus, skin microbiota may provide an adjuvant-like stimulus during vaccination with VACV and influence the host response to vaccination.

Abstract B28: A novel intestinal microbiome-derived peptide modulates immune cell activity and the tumor microenvironment

Abstract The composition of the gut microbiota affects cancer development, progression, and response to therapy. A number of commensal bacteria, including Bifidobacterium, have been associated with increased response to immune checkpoint inhibitors in mouse tumor models, as well as in melanoma patients. We hypothesized that secreted peptides or proteins contribute to the effects mediated by Bifidobacterium strains in vivo. We used our unique bioinformatics-driven discovery platform to nominate putatively secreted Bifidobacterium-derived peptides for evaluation in immune cell effector assays. We have previously described bacterial peptides that induce secretion of proinflammatory cytokines (e.g., IL-6, TNF) by in vitro-generated mouse and human dendritic cells, as well as effector cytokine secretion (e.g., IFNγ, IL-2) by mouse splenic T lymphocytes in vitro. To investigate the function of Bifidobacterium-derived peptides in the context of the tumor microenvironment, we injected a candidate peptide, termed SG-A, directly into the tumors of tumor-bearing mice. We then performed immune phenotyping via the Nanostring PanCancer Immune Profiling panel, as well as by flow cytometry. Both Nanostring and flow cytometry analysis demonstrated an increase in CD45+ lymphocytes within the tumors of mice treated with SG-A. Peptide SG-A also induced upregulation of dendritic cell function genes (CD40, CD83, and CD86) and multiple effector cytokines and chemokines. Restimulation of tumor-draining lymph node cells with a tumor-derived peptide antigen also increased induction of IFNγ in SG-A treated animals (vs. vehicle-treated controls). Collectively, our results demonstrate the utility of the Second Genome discovery platform for leveraging microbiome science to identify novel immunomodulatory factors. This platform offers the potential to identify agents that may complement or enhance efficacy of existing approaches to immunotherapy for melanoma and other cancers. Citation Format: Helena Kiefel, Dhwani Haria, Yuliya Katlinskaya, Divya Ravichandar, Sunit Jain, Thomas Weinmaier, Shoko Iwai, Todd DeSantis, Toshi Takeuchi, Karim Dabbagh, Kareem Graham. A novel intestinal microbiome-derived peptide modulates immune cell activity and the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B28.

Engineering the gut microbiota to treat chronic diseases.

Gut microbes play vital roles in host health and disease. A number of commensal bacteria have been used as vectors for genetic engineering to create living therapeutics. This review highlights recent advances in engineering gut bacteria for the treatment of chronic diseases such as metabolic diseases, cancer, inflammatory bowel diseases, and autoimmune disorders. KEY POINTS: • Bacterial homing to tumors has been exploited to deliver therapeutics in mice models. • Engineered bacteria show promise in mouse models of metabolic diseases. • Few engineered bacterial treatments have advanced to clinical studies.

Abstract 4963: A novel intestinal microbiome-derived peptide modulates immune cell activity and the tumor microenvironment

Abstract The composition of the gut microbiota affects cancer development, progression, and response to therapy. A number of commensal bacteria, including Bifidobacterium, have been associated with increased response to immune checkpoint inhibitors in mouse tumor models and in cancer patients. We hypothesized that secreted peptides or proteins are driving the Bifidobacterium-mediated effects. Using our unique bioinformatic-driven discovery platform we nominated putatively secreted Bifidobacterium-derived peptides for evaluation in immune cell effector assays. We demonstrate that several of the peptides induce secretion of pro-inflammatory cytokines (e.g., IL-6, TNF) by in vitro-generated mouse and human dendritic cells, as well as effector cytokine secretion (e.g., IFNγ, IL-2) by mouse splenic T lymphocytes in vitro. To investigate the function of Bifidobacterium-derived peptides in the context of the tumor microenvironment we injected the candidate peptide SG-A directly into the tumor of CT26 tumor-bearing mice and analyzed the immune phenotype using the Nanostring PanCancer Immune Profiling panel and flow cytometry. Both Nanostring as well as flow cytometry analysis showed an increase in CD45+ tumor-infiltrating lymphocytes in SG-A treated tumors. SG-A peptide also induced the upregulation of dendritic cell function genes (CD40, CD83, and CD86) and multiple effector cytokines and chemokines. Re-stimulation of tumor-draining lymph node cells with AH1 peptide (a CT26 tumor-derived antigen) also increased induction of IFNγ in SG-A treated animals (vs. vehicle-treated controls). Collectively, our results demonstrate the utility of the Second Genome discovery platform for leveraging microbiome science to identify novel immunoregulatory factors. This platform offers a promising approach to identify agents with potential for use as therapeutics in cancer immunotherapy. Citation Format: Helena Kiefel, Dhwani Haria, Yuliya Katlinskaya, Divya Ravichandar, Lily McLaughlin, Sunit Jain, Thomas Weinmaier, Shoko Iwai, Todd DeSantis, Toshi Takeuchi, Karim Dabbagh, Kareem Graham. A novel intestinal microbiome-derived peptide modulates immune cell activity and the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4963.

Helicobacter pylori infection and colorectal carcinoma: is there a causal association?

To the Editor, We would like to thank Dr. Kapetanakis and his colleagues for their interest in our article (1). We specifically appreciate the attention they brought to the importance of environmental factors, particularly Helicobacter pylori (H. pylori) infection, in the development of sporadic colorectal carcinoma (CRC). While the focus of our article was on the pathologic aspects (2), we would like to take this opportunity to extend our discussion to H. pylori as a potential etiopathogenetic factor in colorectal tumorigenesis. As mentioned by Dr. Kapetanakis and his colleagues, the development of sporadic CRC is associated with a variety of environmental factors including diet and lifestyle. Given that the colon harbors the largest number of microorganisms in the body, it is natural to assume that certain microbial species may play a role in colorectal tumorigenesis. The first reports connecting intestinal microflora with CRC were published back in the early 1950s. Streptococcus bovis septicemia was reported to be associated with carcinoma of the sigmoid colon (3). This association was subsequently supported by several publications (4-6). Animal studies have shown that S. bovis or its cell wall antigens promote the formation of hyperproliferative aberrant colonic crypts, enhance the expression of proliferation markers, and increase IL-8 production in the colonic mucosa (7). IL-8 is a proinflammatory cytokine that has been shown to promote the growth, angiogenesis and metastasis of colon cancer cells (8-11). Taken together, these observations suggest that S. bovis acts as a promoter of colorectal tumorigenesis. Later on in the mid-1970s, experiments with germ-free rats further showed that intestinal microflora played a modifying role in colorectal tumorigenesis. Germ-free rats developed much fewer colonic tumors compared to conventional rats when challenged with carcinogens (12,13). Since then, a number of commensal bacteria have been linked to CRC, including Escherichia coli, Enterococcus faecalis, Bacteroides spp. (B. fragilis, B. vulgatus, B. stercoris), Eubacterium limosum, and Clostridium septicum (14-22). Ever since the oncogenic properties of H. pylori were firmly established in the stomach, studies on its oncogenicity have extended to other parts of the gastrointestinal tract, particularly the colon (23). To date, the link between H. pylori infection and CRC remains inconclusive, with some reports showing an association (24-32) while others none (33-37). The results of two meta-analyses published in 2006 and 2008 both suggested a possible small increased risk of CRC in association with H. pylori infection (38,39). Several hypotheses have been proposed to explain the possible link between H. pylori infection and CRC. These include: (I) hypergastrinemia, (II) change in colorectal microflora, (III) toxin production, and (IV) chronic inflammation secondary to direct H. pylori colonization in the colon.

Patented Non-Antibiotic Agents as Animal Feed Additives

For a long time it was a common practice to add subtherapeutic amounts of antibiotics, such as tetracycline, to the feeds of livestock to promote growth and improve productivity. When antibiotic resistance in foodborne human pathogens was reported, this practice was either banned or voluntarily abandoned in many countries. The task of controlling the intestinal microflora in food animals, in the absence of antibiotics, is two-fold. First, to modulate the composition and number of commensal bacteria in the gastrointestinal tract so that it is as favorable as possible to the health and productivity of the animal. Second, to reduce asymptomatic intestinal colonization by pathogenic bacteria in the animals to lower the possibility of foodborne transmission to humans. Unfortunately, the knowledge of what constitutes a healthy, balanced intestinal microflora is still incomplete. This makes the task of favorably changing its composition difficult. However, modulation by means of natural feed supplements has been successfully practised for a number of years, the most important being probiotics, prebiotics, bacteriocins, organic acids, enzymes, bioactive phytochemicals, antimicrobial peptides, lipids and bacteriophages. A number of patents and patent applications have been published recently describing new supplements of various types. Many new compounds can therefore be expected to enter the market in the near future.

Abstract 5457: Chlorinated drinking water alters carcinogenesis in a mice model of colon cancer

Abstract Purpose: The gastrointestinal tract is constantly exposed to vast numbers of commensal bacteria and inflammatory product. The diet and enteric environment has been implicated in the pathogenesis of enterocolitis and colon cancer. Probiotic Lactbacilli modify the enteric microflora and are thought to have a beneficial effect on enterocolitis, eventually on colon cancer. We conducted this study to evaluate the effects of chlorinated drinking water which was used in general institutions. Experimental design: Mouse stains carrying colon epithelium-preferential Apc mutation (CPC;Apc mice), that show sporadic colorectal adenomas and carcinomas are used in this study. Nine of Eighteen CPC;Apc mice were consumed chlorinated drinking water (chlorinate concentrations of 10.0 mg/L) and 9 consumed tap water (chlorinate concentrations of 0.7 mg/L) for 25 week. Body weight was measured weekly. Faecal microbial analysis was performed. At sacrifice, the small and large bowel were histologically assessed. Results: Chlorinated drinking water strongly prevented intestinal tumorigenesis in terms of polyps formation in distal portion of small intestine. However, in colon we observed an increase in numbers and volumes of tumors. Body weight gain was more favorable by chlorine treated. Conclusions: These results show for the first time the efficacy and associated mechanisms of chlorinated drinking water feeding against spontaneous intestinal tumorigenesis in the CPC;Apc mice suggesting its chemopreventive potential against intestinal cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5457. doi:1538-7445.AM2012-5457