microbe Archives - Amazing Health Advances

Diet, Gut Microbes Affect Cancer Treatment Outcomes, Research Suggests

AHA Publisher — Mon, 15 Jun 2020 07:00:10 +0000

University of Virginia Health System via EurekAlert – What we eat can affect the outcome of chemotherapy – and likely many other medical treatments – because of ripple effects that begin in our gut, new research suggests. University of Virginia scientists found that diet can cause microbes in the gut to trigger changes in the host’s response to a chemotherapy drug. Common components of our daily diets (for example, amino acids) could either increase or decrease both the effectiveness and toxicity of the drugs used for cancer treatment, the researchers found. The discovery opens an important new avenue of medical research and could have major implications for predicting the right dose and better controlling the side effects of chemotherapy, the researchers report. The finding also may help explain differences seen in patient responses to chemotherapy that have baffled doctors until now. “The first time we observed that changing the microbe or adding a single amino acid to the diet could transform an innocuous dose of the drug into a highly toxic one, we couldn’t believe our eyes,” said Eyleen O’Rourke, PhD, of UVA’s College of Arts & Sciences, the School of Medicine’s Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. “Understanding, with molecular resolution, what was going on took sieving through hundreds of microbe and host genes. The answer was an astonishingly complex network of interactions between diet, microbe, drug and host.” How Diet Affects Chemotherapy Doctors have long appreciated the importance of nutrition on human health. But the new discovery highlights how what we eat affects not just us but the microorganisms within us. The changes that diet triggers on the microorganisms can increase the toxicity of a chemotherapeutic drug up to 100-fold, the researchers found using the new lab model they created with roundworms. “The same dose of the drug that does nothing on the control diet kills the [roundworm] if a milligram of the amino acid serine is added to the diet,” said Wenfan Ke, a graduate student and lead author of a new scientific paper outlining the findings. Further, different diet and microbe combinations change how the host responds to chemotherapy. “The data show that single dietary changes can shift the microbe’s metabolism and, consequently, change or even revert the host response to a drug,” the researchers report in their paper published in Nature Communications. In short, this means that we eat not just for ourselves but for the more than 1,000 species of microorganisms that live inside each of us, and that how we feed these bugs has a profound effect on our health and the response to medical treatment. One day, doctors may give patients not just prescriptions but detailed dietary guidelines and personally formulated microbe cocktails to help them reach the best outcome. Researchers have observed microbes and diet affecting treatment outcomes before. However, the new research stands out because it is the first time that the underlying molecular processes have been fully dissected. A New Model The researchers’ new model is an extremely simplified version of the complex microbiome – collection of microorganisms – found in people. Roundworms serve as the host, and non-pathogenic E. coli bacteria represent the microbes in the gut. In people, the relationships among diet, microorganisms and host is vastly more complex, and understanding this will be a major task for scientists going forward. The research team noted that drug developers will need to take steps to account for the effect of diet and microbes during their lab work. For example, they will need to factor in whether diet could cause the microorganisms to produce substances, called metabolites, that could interfere or facilitate the effect of the drugs. The researchers suggest that the complexity of the interactions among drug, host and microbiome is likely “astronomical.” Much more study is needed, but the resulting understanding, they say, will help doctors “realize the full therapeutic potential of the microbiota.” “The potential of developing drugs that can improve treatment outcomes by modulating the microbes that live in our gut is enormous,” O’Rourke said. “However, the complexity of the interactions between diet, microbes, therapeutics and the host that we uncovered in this study is humbling. We will need lots of basic research, including sophisticated computer modeling, to reveal how to fully exploit the therapeutic potential of our microbes.” To read the original article click here.

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Bacteria Form Biofilms Like Settlers form Cities

AHA Publisher — Wed, 18 Mar 2020 07:00:39 +0000

University of Pennsylvania via EurekAlert – Microbiologists have long adopted the language of human settlement to describe how bacteria live and grow: They “invade” and “colonize.” Relations dwelling in close proximity are “colonies.” By pairing super-resolution imaging technology with a computational algorithm, a new study in Nature Communications confirms that this metaphor is more apt than scientists may have realized. The findings show that, as individual bacteria multiply and grow into a dense and sticky biofilm, such as the community that forms dental plaque, their growth patterns and dynamics mirror those seen in the growth of cities. “We take this ‘satellite-level’ view, following hundreds of bacteria distributed on a surface from their initial colonization to biofilm formation,” says Hyun (Michel) Koo, a professor in Penn’s School of Dental Medicine and senior author on the work. “And what we see is that, remarkably, the spatial and structural features of their growth are analogous to what we see in urbanization.” This new perspective on how biofilms grow could help inform efforts to either promote the growth of beneficial microbes or break up and kill undesirable biofilms with therapeutics. The idea for the research emerged from conversations among Koo; Geelsu Hwang, a Penn Dental Medicine assistant professor who applies engineering to problems of oral health; and Amauri Paula, a physicist who worked as a visiting professor with Koo’s lab. “Usually when people study biofilms, they analyze a single cell in a narrow field of view as it multiplies, becomes a cluster, and starts to build up,” says Koo. “But we wondered if we followed multiple individual cells simultaneously whether we could identify some patterns at large length-scales.” Hwang developed powerful time-lapse imaging tools, employing confocal laser scanning microscopy capable of analyzing surface topography and tracking bacteria populating a surface down to the individual cell in three dimensions over time. Meanwhile, Paula worked to build an algorithm that could analyze the behavior of this growth over time. For their study, they used the microbe Streptococcus mutans, an oral pathogen responsible for causing cavities when it forms a the biofilm known more commonly as dental plaque and releases acids that decay tooth enamel. They distributed the bacteria on a tooth enamel-like material and followed hundreds of individual microbes during several hours as they divided and grew. Overall, the growth patterns were reminiscent of the formation of urban areas, the team found. Some individual “settlers” grew, expanding into small bacteria “villages.” Then, as the boundaries of the villages grew and, in some cases met, they joined to form larger villages and eventually “cities.” Some of these cities then merged to form larger “megacities.” Surprising the researchers, their results showed that only a subset of the bacteria grew. “We thought that the majority of the individual bacteria would end up growing,” says Koo. “But the actual number was less than 40%, with the rest either dying off or being engulfed by the growth of other microcolonies.” They also didn’t expect a lack of inhibition when this engulfment took place. They thought that, as different microcolonies met, they might compete with one another, causing the two edges to perhaps repel. “Instead they merge and begin to grow as a single unit,” says Koo. On both the individual bacteria and biofilm-wide scale, the researchers confirmed that the gluelike secretion known as extracellular polymeric substances (EPS) enabled bacteria to pack together closely and firmly in the biofilm. When they introduced an enzyme that digested EPS, the communities dissolved and returned to a collection of individual bacteria. “Without EPS, they lose the ability to densely pack and form these ‘cities,'” says Koo. Finally, the researchers experimented to see how the addition of a microbial “friend” or “foe” would influence the original bacteria’s growth. The “foe” was Streptococcus oralis, a bacteria that can inhibit the growth of S. mutans. This addition dramatically impaired the ability of S. mutans to form larger “cities,” like disruptive neighbors that can affect the collective growth of the community. The “friend”–the fungus Candida albicans, which Koo and others have found to interact with S. mutans in biofilms and to contribute to tooth decay–did not affect the biofilm’s growth rate but did help bridge adjacent microcolonies, enabling the development of larger “cities.” Koo cautions about taking the urbanization metaphor of biofilm growth too far but underscores the useful lessons that can result from studying the system holistically and by looking at the events under both “close-up” and “bird’s eye” views. “It’s a useful analogy, but it should be taken with a grain of salt,” Koo says. “We’re not saying these bacteria are anthropomorphic. But taking this perspective of biofilm growth gives us a multiscale, multidimensional picture of how they grow that we’ve not seen before.” To read the original article click here.

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