Tag Archives: Microbiome

Cornell Researchers Develop Tool To Create Maps Of the Locations and Identify Different Microbial Species Including Those That Make Up the Gut Microbiome

Cornell researchers developed an imaging tool to create intricate spatial maps of the locations and identities of hundreds of different microbial species, such as those that make up the gut microbiome. The tool will help scientists understand how complex communities of microorganisms interact with each other and also their environment, which is to say, us.


The team’s paper, “Highly Multiplexed Spatial Mapping of Microbial Communities,” published Dec. 2 in Nature. The paper’s lead author is doctoral student Hao Shi, M.Eng. ’18.

Resource:  https://phys.org/news/2020-12-spatial-view-gut-microbiome.html

“There are communities of bacteria that live in our bodies and play an important role in human health and biology, and there’s a rich diversity of these microbes. We know this from technologies such as DNA sequencing that create lists of the bacterial species that are present in a community,” said Iwijn De Vlaminck, the Robert N. Noyce Assistant Professor in Life Science and Technology in the Meinig School of Biomedical Engineering, and the paper’s senior author.

“However, there are very limited tools to understand the spatial interactions between these microbes, and those are quite clearly important to understand the metabolism of these communities, and also how these microbes interact with their host,” he said.

De Vlaminck and Shi set out to create their imaging method by using a two-step process called high phylogenetic resolution microbiome mapping by fluorescence in situ hybridization (HiPR-FISH). They collaborated with the labs of co-authors Warren Zipfel, associate professor of biomedical engineering, and Ilana Brito, assistant professor and the Mong Family Sesquicentennial Faculty Fellow in Biomedical Engineering, to incorporate additional imaging and microbiome expertise.

To locate the microbial communities, the researchers designed oligonucleotide probes that target specific bacteria cells based on the presence of a signature gene sequence, 16S ribosomal RNA, and they made another group of probes that label the cells with fluorophores. Then the team used confocal microscopy to light up the fluorescent markers with lasers, and they used machine learning and custom software to decode the fluorescence spectra and interpret the images, resulting in an efficient and cost-effective technology with single-cell resolution.

The researchers created the palette for their spatial maps with a mixture of 10 basic colors that could “paint” a total of 1,023 possible color combinations of E. coli, each fluorescently labeled with a unique binary barcode.

“The imaging itself leads to very beautiful, rich images with all bacterial cells in different colors,” De Vlaminck said. “But to allow the quantitative understanding of microbe interactions, the distances between cells, cluster sizes and so on, you need to be able to interpret these in an automated way by a computer so that you can convert this image into a digitized representation of the community.”

The team applied their technology to two different systems: the gut microbiome in mice and the human oral plaque microbiome. In the case of the , they were able to demonstrate how the spatial associations between different bacteria are disrupted by antibiotic treatment.

Spatial mapping could be an important tool for studying and possibly treating a range of diseases in which bacteria are a major culprit, such as inflammatory bowel disease, colorectal cancer, and infection.

“We’d like to dig deeper into the biology of systems where microbiomes play important roles and try to understand how these kinds of spatial dynamics change when you have a disease in progression,” Shi said. “We want to see if that offers any clues and therapeutic insights that we can harness to help people.”

Research Finds Interaction Between an Immune Cell Protein and the Short-Chain Fatty Acids , Produced From Dietary Fiber By Actions Of Gastrointestinal Bacteria, Triggers Protection Against Salmonella Infection

New research in mice has found that a previously unknown interaction between an immune cell protein and the short-chain fatty acids (SCFAs) that are produced from dietary fiber by the actions of gastrointestinal bacteria, triggers protection against infection with Salmonella bacteria.

Reporting their discovery in PLOS Biology, in a paper titled, “Short-chain fatty acids bind to apoptosis-associated speck-like protein to activate inflammasome complex to prevent Salmonella infection,” Hitoshi Tsugawa, Ph.D., of Keio University School of Medicine in Tokyo, Japan, and colleagues say the results could point to new approaches to preventing bacterial infection.

They concluded, “Although further investigation is needed to grasp the precise mechanisms by which dietary fiber and SCFAs modulate intestinal infection, our findings provide new insights into potential therapeutic interventions to prevent pathogenic infections.”

The gastrointestinal microbiome consists of nearly 100 trillion bacteria, comprising more than 1,000 species, the authors wrote. Some of these gut microbial species break down fiber eaten as part of the diet into short-chain fatty acids, which protect against pathogens like Salmonella by influencing the activity of immune cells, including macrophages. “These SCFA-producing bacteria protect against colonization by enteric pathogens, such as Shigella spp., Escherichia coli, and Salmonella spp.,” the authors wrote.

However, the mechanisms by which short-chain fatty acids interact with immune cells remained unclear. “In particular, which molecule(s) in immune cells react with SCFAs to regulate innate immunity remains incompletely understood, and authentic receptors for SCFAs must be identified to reveal their protective mechanisms against pathogen infection,” the team continued.

To better understand the protective role played by SCFAs, the researchers performed a series of laboratory experiments. First, they attached short-chain fatty acids to the surface of synthetic nanobeads, and exposed the structures to the contents of cells that had macrophage characteristics, in order to determine which proteins in the cells interacted with the SCFAs. “This study aimed to identify SCFA receptors that contribute to the regulation of innate immune responses,” they noted. “To this end, we used high-performance affinity nanobeads, which enable direct purification of binding proteins for small-molecule compounds.”

The experiments showed that short-chain fatty acids could bind to a protein called apoptosis-associated speck-like protein (ASC), as a previously unknown interaction. ASC is part of the inflammasome complex, a protein structure that helps to activate the inflammatory response to suppress pathogens. Further studies in macrophages then showed that short-chain fatty acids protected against Salmonella infection by binding to ASC and thereby triggering inflammasome activation.

The tests suggested that the SCFs promote the elimination of S. Typhimurium by recruiting neutrophils into the S. Typhimurium-infected cecal mucosa, by enhancing inflammasome activation in macrophages, and that this macrophage activation is required for ASC-dependent protective effects of SCFAs against the bacterium. “These findings indicated that SCFA-induced ASC-dependent activation of macrophages in the cecal mucosa promotes bacterial elimination to limit bacterial dissemination from the gastrointestinal tract to systemic sites,” the investigators wrote.

The results in mice provide new insights into the effects of dietary fiber on the immune system, although further research will be needed to determine whether the findings are also applicable to humans and to investigate other potential effects of short-chain fatty acids on the immune system. Nevertheless, the authors concluded, “Although further study is needed to clarify the composition profile of gut microbiota associated with the induction of cecal inflammation in response to S. Typhimurium infection, our findings show that SCFAs induce cecal inflammation, which contributes to protection against bacterial infection through an ASC-dependent mechanism.”

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Clinical Trial Study Moving Closer to Having Safe and Effective Products to Restore the Gut Microbiome for Patients with Recurrent C. difficile Infections.

Sahil Khanna, M.B.B.S.

A new study published online in the journal ClinicalInfectious Diseases looked at the use of a non-frozen capsule of microbiome restoration therapy for treating patients with recurrent C. difficile infection.

“Patients with C. difficile are typically managed with antibiotics or fecal transplantation for recurrent C. difficile,” says the study’s author, Sahil Khanna, M.B.B.S., a gastroenterologist at Mayo Clinic. Dr. Khanna says fecal transplantation has been demonstrated to have high success rates by restoring the gut microbiome of patients.  However, he says there are several challenges with fecal transplantation including standardization of the product, keeping it frozen, and mitigating the risk of infectious disease transmission during the procedure. 

To help reduce the risks, Dr. Khanna and his team studied a transplantation method using a non-frozen capsule instead of whole stool transplantation. An initial dose-finding, the investigator-initiated study looked at the efficacy of different doses of fecal matter and the safety of performing microbiome restoration therapy using an oral product, RBX7455 developed by Rebiotix, Inc. The team found no concerns related to safety.

“Our study has several implications,” says Dr. Khanna. “We think that products like capsules may be able to replace fecal transplantation that is currently done via a colonoscopy. We also think that products that are non-frozen may allow for repeat dosing and for patient-administered self-treatment at home. The good news is that we are  moving closer to having safe and effective products to restore the gut microbiome for patients with recurrent C. difficile.”

Dr. Khanna says that larger clinical trials and blinded, placebo-controlled trials are the next step in moving this potential treatment from research into practice.


To read this article in its entirety please click on the following link to be redirected. Thank you. https://advancingthescience.mayo.edu/2020/09/29/study-moves-microbiome-based-therapies-closer-to-the-mainstream-treatment-for-c-difficile-infection/

The 4th Annual Global C. diff. Awareness 2K Walks Go Virtual on September 11 and 12

The 4th Annual Global C.diff. Awareness 2K Walks Will Now Be VIRTUAL!

                   Join Us On……………….

Friday, September 11th – UK

Dr. Clokie, UK Walk Event Coordinator, will be hosting the VIRTUAL Walk in Leicester on September 11th as the UK is also under strict guidelines to slow the spread of the COVID-19 virus. 

  • The Leicester VIRTUAL Walk Will Begin at 10:00 a.m. – 11:00 a.m. – UK

  • VIRTUAL Entertainment Will Begin at 10:00 a.m. UK For the Children!

Saturday, September 12th –  USA

  • The VIRTUAL Walks Will Begin at 9:00 a.m. through 12:00 p.m. EDT

  • VIRTUAL Entertainment Will Begin at 9:00 a.m. EDT For the Children!

All Registered Awareness Walkers Will Receive a T-Shirt, Giveaways, and More via: United States Postal Service To the Address Provided at the Time Of Registration.

To Learn More About the Global C. diff. Awareness Walk Event and How You Can Register, Please Click On the Green Button Below……………..




We are truly grateful for your efforts, support and participation
of the Annual Walk events and we look forward to virtually walking with you in September!

“None of us can do this alone ~ All of us can do this together!”
~ C Diff Foundation

C.difficile (C.diff.) Infections Continue to Grow in Health Care Facilities Worldwide

The burden of Clostridium difficile (C. diff) continues to grow in health care facilities throughout the United States and around the world.

Gaining a better understanding of sources and risk factors for C. diff can help reverse colonization and transmission or prevent it altogether, authors of a new paper suggest.

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“This is a review/commentary article that provides a high-level overview of the literature dealing with C. diff colonization and the microbiome changes associated with C. diff colonization,” author Silvia Munoz-Price, MD, PhD, from the Medical College of Wisconsin in Milwaukee told our sister publication MD Magazine.

After reviewing the literature, authors of the study postulated that when it comes to the potential for C. diff colonization, exposure to and transmissions of the virus occurs outside of hospitals. In fact, it seemed like most of the patients became symptomatic during their hospital stay, rather than acquiring the virus while hospitalized.

For example, the investigators cited one study from Canada that had been conducted from 2006 to 2007 where more than 4000 patients were screened for C. diff colonization upon hospitalization, during their stay (on a weekly basis) and at discharge. They found that 4% of the patients were colonized upon hospitalization and 3% acquired C. diff during their stay in the hospital.

The authors also found evidence indicating that community-acquired C. diff appears to be on the rise. The authors discuss a decade-long study which took place in Minnesota where community-acquired C. diff infection rates rose from 2.8 to 14.9 per 100,000-person-years within the 10-year span. The patients in that study more likely to acquire C. diff were younger, female, and healthier than patients with hospitalization acquired C. diff. The reviewers also said that rates of community-acquired C. diff have also been rising in Finland, Australia, and England, according to published studies.

Most of the common risk factors for community-acquired C. diff infections still applied, the researchers found, including antibiotic exposure, household contact, and animals. A 2013 study showed that two-thirds of community-acquired C. difficile patients were exposed to antibiotics in the preceding 12 weeks of their infection, and about one-third had been exposed to proton pump inhibitors.

While studies examining transmissibility within households are difficult to come by, the study authors found one review from Quebec. The review consisted of 2222 cases of C. diff diagnosed between 1998 and 2009, and investigators found that 8 cases were designated to be transmitted by household contacts. However, the researchers noted, confirmation using strain typing was not performed in that study.

Looking at farm livestock, a 2013 Dutch study showed that individuals with daily contact with pigs showed rates of C. diff positivity of 25%; in those with weekly contact, it was 14%. In the same study, C. diff was found in the manure from all the farms in 10% to 80% of the samples per farm. The reviewers also said that C. diff has been found in the stool of farm chickens, calves, and retail ground meat. Dogs and cats are also known to culture positive for C. diff, and the researchers wrote that the bacteria can also be present in vegetables and water (tap water, swimming pools, as well as rivers, lakes, and seas). They hypothesized that the presence of C. diff in vegetables may come from the use of organic fertilizer.

“We envision that in the future we should be able to take advantage of our increasing knowledge about microbiome changes so that we will be able to: identify patients at risk for de novo C. difficile colonization during their hospitalization and manipulate our patients’ microbiome to prevent or reverse C. difficile colonization,” Dr. Munoz-Price said.

“Different from what we do now, the latter would be accomplished not by withholding or changing antibiotics but by correcting the deficient flora of a patient in an individualized fashion. This new approach would revolutionize the field of Infection Control and Antibiotic Stewardship,” she concluded.