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Bacteriophages may play role in Parkinson’s disease

ATLANTA — Researchers have discovered substantial differences in the abundance of bacteriophages in patients with Parkinson’s disease compared with people who do not have the neurodegenerative disorder.

The findings indicate bacteriophages may be an “overlooked driver” of Parkinson’s disease (PD) and a potential therapeutic target, according to George Tetz, MD, PhD, CEO of the Human Microbiology Institute (HMI), a nonprofit, multidisciplinary microbiome-focused organization based in New York.

“Our research is the first to show the role of bacterial viruses (bacteriophages) as human pathogens,” he told Infectious Disease News.

For the study, Tetz and colleagues analyzed the fecal microbiome of 32 patients with PD and 28 healthy controls. Their objective was to identify alterations in the microbiota that may be associated with PD onset or progression.

A comparative analysis of the bacterial and bacteriophage community compositions revealed significant reductions in Lactococcus species, Streptococcus species and Lactobacillus species among patients with PD. These bacteria, according to the researchers, are a key source of microbiota-derived neurochemicals, including dopamine, which has a critical role in PD.

Tetz and colleagues found that the abundance of neurotransmitter-producing Lactococcus species was more than 10 times lower among patients with PD, indicating phages may play a role in neurodegeneration.

In healthy controls, there was a similar balance of lytic and temperate Lactococcus phages, whereas, in patients with PD, most Lactococcus phages were lytic, virulent phages, which Tetz said could explain the overall depletion of Lactococcus species in these patients.

“The depletion of Lactococcus due to high numbers of strictly lytic phages in PD patients might be associated with PD development and directly linked to dopamine decrease as well as the development of gastrointestinal symptoms of PD,” Tetz said in a press release.

The lytic Lactococcus phages in patients with PD belonged to phage groups that are often isolated from dairy products. This finding, Tetz and colleagues reported, highlights the need to assess the role of environmental phages in patient health.

Tetz said there may be several reasons for the increased abundance of lytic Lactococcus phages among patients with PD. One could be related to an altered sensitivity to environmental Lactococcus phages.

“Notably, Lactococcus species are known to possess abortive infection systems, also known as phage exclusion systems, that block phage multiplication, leading to premature bacterial death following phage infection,” he told Infectious Disease News. “Thus, the number of progeny phage particles decreases, limiting the spread of phages to other bacteria within the population and allowing the bacterial population to survive. It is suggested that phages in PD have developed mechanisms to overcome these antiphage systems; however, additional studies are required to confirm this.”

Moving forward, Tetz said his team will examine the role of phages as novel, therapeutic targets for PD, as well as novel diagnostic systems for early stages of PD diagnosis.

“We believe that the discovery of bacteriophages as human pathogens has been previously overlooked and is the next transformative step in neuromedicine,” he said. “HMI is currently the only company developing novel targeted antibacteriophage programs, based on our submitted-patent technologies that cover antiphage treatments, prevention of phages’ negative effects, as well as the modification of phage-bacteria interplay and can be used for both treatment and prevention of different neurodegenerative pathologies.” – by Stephanie Viguers

Reference:

Tetz G, et al. Abstract 117. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.

Disclosures: The researchers report no relevant financial disclosures.

ATLANTA — Researchers have discovered substantial differences in the abundance of bacteriophages in patients with Parkinson’s disease compared with people who do not have the neurodegenerative disorder.

The findings indicate bacteriophages may be an “overlooked driver” of Parkinson’s disease (PD) and a potential therapeutic target, according to George Tetz, MD, PhD, CEO of the Human Microbiology Institute (HMI), a nonprofit, multidisciplinary microbiome-focused organization based in New York.

“Our research is the first to show the role of bacterial viruses (bacteriophages) as human pathogens,” he told Infectious Disease News.

For the study, Tetz and colleagues analyzed the fecal microbiome of 32 patients with PD and 28 healthy controls. Their objective was to identify alterations in the microbiota that may be associated with PD onset or progression.

A comparative analysis of the bacterial and bacteriophage community compositions revealed significant reductions in Lactococcus species, Streptococcus species and Lactobacillus species among patients with PD. These bacteria, according to the researchers, are a key source of microbiota-derived neurochemicals, including dopamine, which has a critical role in PD.

Tetz and colleagues found that the abundance of neurotransmitter-producing Lactococcus species was more than 10 times lower among patients with PD, indicating phages may play a role in neurodegeneration.

In healthy controls, there was a similar balance of lytic and temperate Lactococcus phages, whereas, in patients with PD, most Lactococcus phages were lytic, virulent phages, which Tetz said could explain the overall depletion of Lactococcus species in these patients.

“The depletion of Lactococcus due to high numbers of strictly lytic phages in PD patients might be associated with PD development and directly linked to dopamine decrease as well as the development of gastrointestinal symptoms of PD,” Tetz said in a press release.

The lytic Lactococcus phages in patients with PD belonged to phage groups that are often isolated from dairy products. This finding, Tetz and colleagues reported, highlights the need to assess the role of environmental phages in patient health.

Tetz said there may be several reasons for the increased abundance of lytic Lactococcus phages among patients with PD. One could be related to an altered sensitivity to environmental Lactococcus phages.

“Notably, Lactococcus species are known to possess abortive infection systems, also known as phage exclusion systems, that block phage multiplication, leading to premature bacterial death following phage infection,” he told Infectious Disease News. “Thus, the number of progeny phage particles decreases, limiting the spread of phages to other bacteria within the population and allowing the bacterial population to survive. It is suggested that phages in PD have developed mechanisms to overcome these antiphage systems; however, additional studies are required to confirm this.”

Moving forward, Tetz said his team will examine the role of phages as novel, therapeutic targets for PD, as well as novel diagnostic systems for early stages of PD diagnosis.

“We believe that the discovery of bacteriophages as human pathogens has been previously overlooked and is the next transformative step in neuromedicine,” he said. “HMI is currently the only company developing novel targeted antibacteriophage programs, based on our submitted-patent technologies that cover antiphage treatments, prevention of phages’ negative effects, as well as the modification of phage-bacteria interplay and can be used for both treatment and prevention of different neurodegenerative pathologies.” – by Stephanie Viguers

Reference:

Tetz G, et al. Abstract 117. Presented at: ASM Microbe; June 7-11, 2018; Atlanta.

Disclosures: The researchers report no relevant financial disclosures.

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