December 13, 2017
Georgia State University
Lactic acid bacteria, commonly used as probiotics to
improve digestive health, can offer protection against different subtypes of
influenza A virus, resulting in reduced weight loss after virus infection and
lower amounts of virus replication in the lungs, according to a new study.
Lactic acid bacteria, commonly used as probiotics to improve digestive
health, can offer protection against different subtypes of influenza A virus,
resulting in reduced weight loss after virus infection and lower amounts of
virus replication in the lungs, according to a study led by Georgia State
Influenza virus can cause severe respiratory disease in humans. Although
vaccines for seasonal influenza viruses are readily available, influenza virus
infections cause three to five million life-threatening illnesses and 250,000
to 500,000 deaths worldwide during epidemics. Pandemic outbreaks and air
transmission can rapidly cause severe disease and claim many more human lives
worldwide. This occurs because current vaccines are effective only when vaccine
strains and circulating influenza viruses are well matched.
Influenza A virus, which infects humans, birds and pigs, has many different
subtypes based on hemagglutinin (HA) and neuraminidase (NA) proteins on the
surface of the virus. There are 18 different HA and 11 different NA subtype
molecules identified, which indicates numerous HA and NA influenza virus
combinations. As a result, it’s important to find ways to provide broad
protection against influenza viruses, regardless of the virus strain.
Fermented vegetables and dairy products contain a variety of lactic acid
bacteria, which have a number of health benefits in addition to being used as
probiotics. Studies have found some lactic acid bacteria strains provide
partial protection against bacterial infectious diseases, such as Streptococcus
pneumoniae, as well as cold and influenza viruses.
This study investigated the antiviral protective effects of a heat-killed
strain of lactic acid bacteria, Lactobacillus casei DK128 (DK128), a
promising probiotic isolated from fermented vegetables, on influenza viruses.
Mice pretreated with DK128 intranasally and infected with influenza A virus
showed a variety of immune responses that are correlated with protection
against influenza virus, including an increase in the alveolar macrophage cells
in the lungs and airways, early induction of virus specific antibodies and
reduced levels of pro-inflammatory cytokines and innate immune cells. The mice
also developed immunity against secondary influenza virus infection by other
virus subtypes. The findings are published in the journal Scientific Reports.
“We found that pretreating the mice with heat-killed Lactobacillus
casei DK128 bacteria made them resistant to lethal primary and secondary
influenza A virus infection and protected them against weight loss and
mortality,” said Dr. Sang-Moo Kang, lead author of the study and professor
in the Institute for Biomedical Sciences at Georgia State. “Our results
are highly significant because mice pretreated with DK128 had 100 percent
survival and prevention of weight loss. This strain of lactic acid bacteria
also equipped mice with cross-protective immunity against secondary lethal
infection with influenza virus. Protection against influenza virus infection
was not specific to a particular strain of influenza.
“Our study provides evidence that heat-killed lactic acid bacteria
could potentially be administered via a nasal spray as a prophylactic drug
against non-specific influenza virus infections.”
The researchers pretreated mice intranasally with heat-killed DK128 and
then infected them with a lethal dose of influenza A virus, subtype H3N2 or
H1N1. Mice pretreated with a low dose of DK128 showed 10 to 12 percent weight
loss, but survived the lethal infection of H3N2 or H1N1 virus. In contrast,
mice pretreated with a higher dose of heat-killed DK128 did not show weight
loss. Control mice, which were not pretreated with DK128, showed severe weight
loss by days eight and nine of the infection and all of these mice died.
Mice that received heat-killed lactic acid bacteria (DK128) prior to
infection had about 18 times less influenza virus in their lungs compared to
Next, the researchers tested protection against secondary influenza virus
infection by infecting pretreated mice with a different influenza A subtype
from their primary virus infection. For the secondary virus infection, mice
were exposed to H1N1 or rgH5N1.
The study’s results suggest that pretreatment with lactic acid bacteria,
specifically DK128, equips mice with the capacity to have protective immunity
against a broad range of primary and secondary influenza A virus infections.
Co-authors of the study include Drs. Yu-Jin Jung, Young-Tae Lee, Vu Le Ngo,
Eun-Ju Ko and Ki-Hye Kim of the Institute for Biomedical Sciences at Georgia
State; Drs. Young-Hee Cho, Sung-Moon Hong, Cheol-Hyun Kim of Dankook
University; Drs. Ji-Hun Jang and Joon-Suk Oh of Tobico Inc.; Dr. Min-Kyung Park
of Chungwoon University and Dr. Jun Sun of the University of Illinois at
The study is funded by the National Institute of Allergy and Infectious
Diseases and the National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health and the United States Department
Young-Tae Lee, Vu Le Ngo, Young-Hee Cho, Eun-Ju Ko, Sung-Moon Hong, Ki-Hye Kim,
Ji-Hun Jang, Joon-Suk Oh, Min-Kyung Park, Cheol-Hyun Kim, Jun Sun, Sang-Moo
Kang. Heat-killed Lactobacillus casei confers broad protection against
influenza A virus primary infection and develops heterosubtypic immunity
against future secondary infection. Scientific Reports, 2017; 7 (1)