Page 62 - Read Online

Jiang et al. Microbiome Res Rep 2024;3:47 https://dx.doi.org/10.20517/mrr.2024.12 Page 15 of 20

some are DSS-induced mouse models and some are knockout mouse models - and the different amounts of
Akk administrated. In addition, there are differences in the specificity of the strains used: different strains of
the same species may have opposite effects in the same disease. Most current studies on Akk are limited to
the model strain isolated in 2004, ATCC BAA-835T. However, another newly isolated strain of Akk in 2017
has been shown to exacerbate colitis in IL-10 / mice. In addition, a study in 2019 reported differences in
- -
anti-inflammatory function between Akk BAA-835T and mouse-derived Akk strain 139. Therefore, the
strain specificity of Akk may also be the main reason for the different results of different experiments. The
pro-inflammatory effect of lipid components of Akk has recently been discovered. As membrane
phospholipids from Akk can induce BMDCs to produce pro-inflammatory cytokines such as TNF-α in a
[109]
TLR2-dependent manner . Furthermore, similar to intestinal inflammation, the role of Akk in CRC is
controversial. A recent study in 2022 found that receiving Akk administration exacerbated the development
of colitis-associated CRC in AOM/DSS-induced model mice, as evidenced by shorter colon length, more
[110]
severe weight loss, and more intestinal tumors . There are multiple possible reasons to explain the
differences in the results of different experiments. First, the viability of Akk, the frequency of administration,
and the number of bacteria, all affect Akk colonization and CRC development. Furthermore, the role of Akk
may be different in different CRC models. The classical AOM/DSS-induced CRC model was chosen in this
study in 2022, which may be different from the spontaneous CRC models such as APC / mice in other
min +
studies. More studies are required in the future to explore and confirm the role of Akk in intestinal tumors
and intestinal inflammation. In addition, future studies on Akk should pay detailed attention to the strains
and evaluation of the probiotic effect of each type of Akk strain. So far, there is still a lack of relevant
research on whether Akk has adverse effects on intestinal functional diseases and metabolic diseases. In this
context, the probiotic role of Akk in intestinal-related diseases and its specific mechanisms need to be
explored further in the future.

CONCLUSION AND PERSPECTIVE
In summary, as a paradigm in the new generation of probiotics, the colonization of Akk in the intestine is
closely related to maintaining intestinal homeostasis. It plays a critical role in the progression and treatment
design of intestinal inflammation, cancer, and other diseases caused by intestinal disorders, such as liver
diseases and diabetes. While the majority of research indicates the beneficial effects of Akk treatment, some
studies suggest it may exacerbate disease progression. This discrepancy could be attributed to variations
across studies, such as differing disease models, the distinct intestinal environments in which Akk operates,
the activity levels of various Akk strains, or the specific components of Akk used. It is worth mentioning that
the extracellular vesicles and proteins of Akk are increasingly well studied, and studies have shown that
these components may be more protective when used alone than active organisms, which is more suitable
for clinical applications. In addition, pasteurized intact Akk cells are considered safe for human
consumption and thus are suitable for clinical application. They have been shown to be as effective or even
more effective than living cells in the treatment of metabolic disorders. Therefore, it is of interest to
continue exploring the pasteurized cells, extracellular vesicles, and bacterial outer membrane fractions of
Akk to extract and utilize the fractions that play an important role. Furthermore, studies on the brain-gut
axis and lung-gut axis have been emerging in recent years, and in addition to metabolic and liver diseases,
the association between intestinal homeostasis and other systemic diseases is gaining more attention, and
future studies may explore the role of Akk in other diseases in the future. In conclusion, as a potential
probiotic, Akk is stably colonized in the intestine, and there is substantial evidence of its positive effects on
intestinal-related diseases. Further evaluation of Akk’s safety, or the development of its active ingredient for
targeted drug delivery, could pave the way for its clinical application as a therapeutic agent. Additionally,
probiotic enzymes could be defined as prokaryotic isoenzymes from intestinal bacteria, which catalyze
eukaryotic targets from host cells and function as potential drugs. As probiotic enzymes from Akk, both