TBD Meeting (3042-20)

For seriously ill patients with multidrug-resistant organisms (MDROs) in their gastrointestinal tract, performing a fecal microbiota transplant (FMT) may result in fewer and less severe infections, as well as shorter hospital stays, according to investigators.

Significant clinical improvements were observed across the group even though 59% of patients did not clear MDROs, which suggests that complete decolonization of resistant organisms may be unnecessary for patients to benefit from FMT, reported lead author Julian Marchesi, PhD, of Cardiff (Wales) University and Imperial College London (England).

“We see the quality of life for these patients is hugely improved even when we don’t get rid of the organism totally,” Dr. Marchesi said in a virtual press conference.

Although previous studies have suggested that FMT may be used to decolonize MDROs, little research has addressed other clinical outcomes, the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

The present study involved 20 patients with MDROs, including extended-spectrum beta-lactamase Enterobacteriaceae (ESBL), carbapenemase-producing Enterobacteriaceae (CPE), or vancomycin-resistant enterococci (VRE). Approximately half of the population (n = 11) had chronic hematological disease. The other half (n = 9) had recurrent urinary tract infections with ESBL, including patients who had undergone renal transplant or had recurrent Clostridioides difficile infection.

For each transplant, 200-300 mL of fecal slurry was delivered via nasogastric tube into the small intestine. Fecal donors underwent a strict screening process that included blood, fecal, and behavioral testing.

Multiple clinical outcomes were evaluated in the 6 months leading up to FMT, then compared with outcomes in the 6 months following fecal transplant. Out of 20 patients, 17 completed the 6-month follow-up. Although only 7 of these patients (41%) were decolonized of MDROs, multiple significant clinical improvements were observed across the group, including reductions in MDRO bloodstream infections (P = .047), all bloodstream infections (P = .03), length of stay in hospital (P = .0002), and duration of carbapenem use (P = .0005). Eight out of 11 patients with hematologic disease improved enough to undergo stem cell transplantation within 6 months of FMT, and in the subgroup of patients who had undergone renal transplant, the rate of urinary tract infections was significantly improved (P = .008).

No serious adverse events were encountered during the trial, which led the investigators to conclude that FMT was safe and well tolerated, even in patients with bloodstream infections and those who were highly immunosuppressed.

Beyond clinical implications, Dr. Marchesi suggested that the study findings should influence FMT trial methodology.

“We’ve got to start thinking a little bit differently in terms of how we measure the impact of FMT,” he said. “It’s not all about ... getting rid of these opportunistic pathogens. There are other quality-of-life factors that we need to measure, because they’re also important for the patient.”

Dr. Marchesi said that more research is needed to confirm findings and gain a mechanistic understanding of why patients may improve despite a lack of decolonization.

“We think we’re on a strong foundation here to take this into a clinical trial,” he said.

The research was funded by the National Institute for Health Research and the Medical Research Council. The investigators reported no conflicts of interest.

For seriously ill patients with multidrug-resistant organisms (MDROs) in their gastrointestinal tract, performing a fecal microbiota transplant (FMT) may result in fewer and less severe infections, as well as shorter hospital stays, according to investigators.

Significant clinical improvements were observed across the group even though 59% of patients did not clear MDROs, which suggests that complete decolonization of resistant organisms may be unnecessary for patients to benefit from FMT, reported lead author Julian Marchesi, PhD, of Cardiff (Wales) University and Imperial College London (England).

“We see the quality of life for these patients is hugely improved even when we don’t get rid of the organism totally,” Dr. Marchesi said in a virtual press conference.

Although previous studies have suggested that FMT may be used to decolonize MDROs, little research has addressed other clinical outcomes, the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

The present study involved 20 patients with MDROs, including extended-spectrum beta-lactamase Enterobacteriaceae (ESBL), carbapenemase-producing Enterobacteriaceae (CPE), or vancomycin-resistant enterococci (VRE). Approximately half of the population (n = 11) had chronic hematological disease. The other half (n = 9) had recurrent urinary tract infections with ESBL, including patients who had undergone renal transplant or had recurrent Clostridioides difficile infection.

For each transplant, 200-300 mL of fecal slurry was delivered via nasogastric tube into the small intestine. Fecal donors underwent a strict screening process that included blood, fecal, and behavioral testing.

Multiple clinical outcomes were evaluated in the 6 months leading up to FMT, then compared with outcomes in the 6 months following fecal transplant. Out of 20 patients, 17 completed the 6-month follow-up. Although only 7 of these patients (41%) were decolonized of MDROs, multiple significant clinical improvements were observed across the group, including reductions in MDRO bloodstream infections (P = .047), all bloodstream infections (P = .03), length of stay in hospital (P = .0002), and duration of carbapenem use (P = .0005). Eight out of 11 patients with hematologic disease improved enough to undergo stem cell transplantation within 6 months of FMT, and in the subgroup of patients who had undergone renal transplant, the rate of urinary tract infections was significantly improved (P = .008).

No serious adverse events were encountered during the trial, which led the investigators to conclude that FMT was safe and well tolerated, even in patients with bloodstream infections and those who were highly immunosuppressed.

Beyond clinical implications, Dr. Marchesi suggested that the study findings should influence FMT trial methodology.

“We’ve got to start thinking a little bit differently in terms of how we measure the impact of FMT,” he said. “It’s not all about ... getting rid of these opportunistic pathogens. There are other quality-of-life factors that we need to measure, because they’re also important for the patient.”

Dr. Marchesi said that more research is needed to confirm findings and gain a mechanistic understanding of why patients may improve despite a lack of decolonization.

“We think we’re on a strong foundation here to take this into a clinical trial,” he said.

The research was funded by the National Institute for Health Research and the Medical Research Council. The investigators reported no conflicts of interest.

For seriously ill patients with multidrug-resistant organisms (MDROs) in their gastrointestinal tract, performing a fecal microbiota transplant (FMT) may result in fewer and less severe infections, as well as shorter hospital stays, according to investigators.

Significant clinical improvements were observed across the group even though 59% of patients did not clear MDROs, which suggests that complete decolonization of resistant organisms may be unnecessary for patients to benefit from FMT, reported lead author Julian Marchesi, PhD, of Cardiff (Wales) University and Imperial College London (England).

“We see the quality of life for these patients is hugely improved even when we don’t get rid of the organism totally,” Dr. Marchesi said in a virtual press conference.

Although previous studies have suggested that FMT may be used to decolonize MDROs, little research has addressed other clinical outcomes, the investigators wrote in an abstract released as part of the annual Digestive Disease Week®, which was canceled because of COVID-19.

The present study involved 20 patients with MDROs, including extended-spectrum beta-lactamase Enterobacteriaceae (ESBL), carbapenemase-producing Enterobacteriaceae (CPE), or vancomycin-resistant enterococci (VRE). Approximately half of the population (n = 11) had chronic hematological disease. The other half (n = 9) had recurrent urinary tract infections with ESBL, including patients who had undergone renal transplant or had recurrent Clostridioides difficile infection.

For each transplant, 200-300 mL of fecal slurry was delivered via nasogastric tube into the small intestine. Fecal donors underwent a strict screening process that included blood, fecal, and behavioral testing.

Multiple clinical outcomes were evaluated in the 6 months leading up to FMT, then compared with outcomes in the 6 months following fecal transplant. Out of 20 patients, 17 completed the 6-month follow-up. Although only 7 of these patients (41%) were decolonized of MDROs, multiple significant clinical improvements were observed across the group, including reductions in MDRO bloodstream infections (P = .047), all bloodstream infections (P = .03), length of stay in hospital (P = .0002), and duration of carbapenem use (P = .0005). Eight out of 11 patients with hematologic disease improved enough to undergo stem cell transplantation within 6 months of FMT, and in the subgroup of patients who had undergone renal transplant, the rate of urinary tract infections was significantly improved (P = .008).

No serious adverse events were encountered during the trial, which led the investigators to conclude that FMT was safe and well tolerated, even in patients with bloodstream infections and those who were highly immunosuppressed.

Beyond clinical implications, Dr. Marchesi suggested that the study findings should influence FMT trial methodology.

“We’ve got to start thinking a little bit differently in terms of how we measure the impact of FMT,” he said. “It’s not all about ... getting rid of these opportunistic pathogens. There are other quality-of-life factors that we need to measure, because they’re also important for the patient.”

Dr. Marchesi said that more research is needed to confirm findings and gain a mechanistic understanding of why patients may improve despite a lack of decolonization.

“We think we’re on a strong foundation here to take this into a clinical trial,” he said.

The research was funded by the National Institute for Health Research and the Medical Research Council. The investigators reported no conflicts of interest.

Altering the gut microbiome may reduce the tumor-promoting effects of cigarette smoking, based on a preclinical study.

Mice treated with microbiome-depleting antibiotics or genetically modified to lack an adaptive immune response did not show increased rates of cancer growth when exposed to cigarette smoke, reported lead author Prateek Sharma, MBBS, of the University of Miami, and colleagues.

Although previous research has shown that the gut microbiome plays a role in the progression of cancer and that smoking alters the gut microbiome, the collective effects of these changes have not been studied, the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

“There is information that smoking changes the gut microbiome ... but the impact of this change is not known,” Dr. Sharma said in a virtual press conference.

To learn more, the investigators first performed an experiment using wild-type mice. All mice were injected with a cancer cell line from the pancreas, colon, or bladder. Mice were then sorted into four groups, in which they were given microbiome-depleting antibiotics and exposed to smoke, given antibiotics alone, exposed to smoke alone, or left untreated and unexposed to serve as controls. Tumor size was then measured over the course of 2 months.

The experiment revealed that mice exposed to smoke but not treated with antibiotics had increased rates of tumor growth regardless of cancer type. But in mice treated with antibiotics, the tumor-promoting effects of smoke exposure were completely lost; the mice had rates of tumor growth even lower than controls.

This experiment was repeated with mice genetically engineered to lack an adaptive immune response. Regardless of smoke or antibiotic exposure, all mice had comparable rates of tumor growth.

Dr. Sharma offered a summary of the findings and their possible implications for human medicine.

“Cigarette smoking changes the gut microbiome, and this changed gut microbiome interacts with the immune system to affect cancer progression,” he said. “If we can target this changed microbiome with modulation strategies like antibiotics, probiotics, or administration of good bacteria, we can alter this process. And if the same results are found in human studies, it could go a long way to affect cancer outcomes in smokers.”

In addition to human studies, Dr. Sharma said that future research should aim to uncover the underlying mechanisms involved in this process, including the types of bacteria that play a role.

When asked if the study might lessen concerns about the negative impacts of smoking among cancer patients, Dr. Sharma suggested that, even if the findings do translate to humans, smoking would still carry significant health risks.

“Even if gut microbiome modulation strategies do work in these patients, it may help a little, but it’s not going to bring it down to the level of nonsmokers, so it’s no way an excuse to not fear or continue [smoking],” he said.

The study was funded by the Florida Department of Health. The investigators reported no conflicts of interest.

Altering the gut microbiome may reduce the tumor-promoting effects of cigarette smoking, based on a preclinical study.

Mice treated with microbiome-depleting antibiotics or genetically modified to lack an adaptive immune response did not show increased rates of cancer growth when exposed to cigarette smoke, reported lead author Prateek Sharma, MBBS, of the University of Miami, and colleagues.

Although previous research has shown that the gut microbiome plays a role in the progression of cancer and that smoking alters the gut microbiome, the collective effects of these changes have not been studied, the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

“There is information that smoking changes the gut microbiome ... but the impact of this change is not known,” Dr. Sharma said in a virtual press conference.

To learn more, the investigators first performed an experiment using wild-type mice. All mice were injected with a cancer cell line from the pancreas, colon, or bladder. Mice were then sorted into four groups, in which they were given microbiome-depleting antibiotics and exposed to smoke, given antibiotics alone, exposed to smoke alone, or left untreated and unexposed to serve as controls. Tumor size was then measured over the course of 2 months.

The experiment revealed that mice exposed to smoke but not treated with antibiotics had increased rates of tumor growth regardless of cancer type. But in mice treated with antibiotics, the tumor-promoting effects of smoke exposure were completely lost; the mice had rates of tumor growth even lower than controls.

This experiment was repeated with mice genetically engineered to lack an adaptive immune response. Regardless of smoke or antibiotic exposure, all mice had comparable rates of tumor growth.

Dr. Sharma offered a summary of the findings and their possible implications for human medicine.

“Cigarette smoking changes the gut microbiome, and this changed gut microbiome interacts with the immune system to affect cancer progression,” he said. “If we can target this changed microbiome with modulation strategies like antibiotics, probiotics, or administration of good bacteria, we can alter this process. And if the same results are found in human studies, it could go a long way to affect cancer outcomes in smokers.”

In addition to human studies, Dr. Sharma said that future research should aim to uncover the underlying mechanisms involved in this process, including the types of bacteria that play a role.

When asked if the study might lessen concerns about the negative impacts of smoking among cancer patients, Dr. Sharma suggested that, even if the findings do translate to humans, smoking would still carry significant health risks.

“Even if gut microbiome modulation strategies do work in these patients, it may help a little, but it’s not going to bring it down to the level of nonsmokers, so it’s no way an excuse to not fear or continue [smoking],” he said.

The study was funded by the Florida Department of Health. The investigators reported no conflicts of interest.

Altering the gut microbiome may reduce the tumor-promoting effects of cigarette smoking, based on a preclinical study.

Mice treated with microbiome-depleting antibiotics or genetically modified to lack an adaptive immune response did not show increased rates of cancer growth when exposed to cigarette smoke, reported lead author Prateek Sharma, MBBS, of the University of Miami, and colleagues.

Although previous research has shown that the gut microbiome plays a role in the progression of cancer and that smoking alters the gut microbiome, the collective effects of these changes have not been studied, the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

“There is information that smoking changes the gut microbiome ... but the impact of this change is not known,” Dr. Sharma said in a virtual press conference.

To learn more, the investigators first performed an experiment using wild-type mice. All mice were injected with a cancer cell line from the pancreas, colon, or bladder. Mice were then sorted into four groups, in which they were given microbiome-depleting antibiotics and exposed to smoke, given antibiotics alone, exposed to smoke alone, or left untreated and unexposed to serve as controls. Tumor size was then measured over the course of 2 months.

The experiment revealed that mice exposed to smoke but not treated with antibiotics had increased rates of tumor growth regardless of cancer type. But in mice treated with antibiotics, the tumor-promoting effects of smoke exposure were completely lost; the mice had rates of tumor growth even lower than controls.

This experiment was repeated with mice genetically engineered to lack an adaptive immune response. Regardless of smoke or antibiotic exposure, all mice had comparable rates of tumor growth.

Dr. Sharma offered a summary of the findings and their possible implications for human medicine.

“Cigarette smoking changes the gut microbiome, and this changed gut microbiome interacts with the immune system to affect cancer progression,” he said. “If we can target this changed microbiome with modulation strategies like antibiotics, probiotics, or administration of good bacteria, we can alter this process. And if the same results are found in human studies, it could go a long way to affect cancer outcomes in smokers.”

In addition to human studies, Dr. Sharma said that future research should aim to uncover the underlying mechanisms involved in this process, including the types of bacteria that play a role.

When asked if the study might lessen concerns about the negative impacts of smoking among cancer patients, Dr. Sharma suggested that, even if the findings do translate to humans, smoking would still carry significant health risks.

“Even if gut microbiome modulation strategies do work in these patients, it may help a little, but it’s not going to bring it down to the level of nonsmokers, so it’s no way an excuse to not fear or continue [smoking],” he said.

The study was funded by the Florida Department of Health. The investigators reported no conflicts of interest.

First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.

In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.

The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”

Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.

“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”

The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.

Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.

“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.

Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.

The investigators reported no outside funding or conflicts of interest.

SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.

First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.

In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.

The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”

Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.

“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”

The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.

Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.

“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.

Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.

The investigators reported no outside funding or conflicts of interest.

SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.

First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.

In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.

The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”

Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.

“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”

The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.

Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.

“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.

Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.

The investigators reported no outside funding or conflicts of interest.

SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.