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Microbes & Immunity Hydrogen alleviates non-alcoholic fatty liver disease

were significant differences in the abundance of important dynamic balance to some extent and play an important
microorganisms in the mouse intestine among the three role in the progression of obesity, metabolic syndrome,
groups according to the analysis of the evolutionary clade and NAFLD. Dysbiosis of the gut flora is known to lead
tree (Figure 3F). The Firmicutes-to-Bacteroidia ratio (FBR) to impaired intestinal barrier function and associated
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of the HFD group was significantly greater than that of immune responses. Our results showed that compared
the control group (P < 0.001) (Figure 3H and I). The FBR with the control group, the abundances of Faecalibaculum
of the HFD + H group was lower than that of the HFD and Coriobacteriaceae_UCG-002 significantly increased
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group (P < 0.01) but higher than that of the control group in the intestinal tract of HFD group mice, and the FBR of
(P < 0.01) (Figure 3I). Compared to that in the control the HFD group also increased significantly. Moreover, the
group, the population of A. muciniphila in the intestinal relative abundance of A. muciniphila in the intestinal flora
flora of the HFD group was almost decimated (P < 0.0001). of the HFD group almost disappeared compared to that
Surprisingly, the relative abundance of A. muciniphila in in the control group (P < 0.0001), suggesting that HFD
the HFD + H group increased significantly compared induced structural changes of intestinal flora.
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with that in the HFD group (P < 0.05), although it still did A. muciniphila, a gram-negative anaerobic bacterium,
not restore to the same level as in the control group (P < was successfully isolated in 2004. It is also the only
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0.0001) (Figure 3L and M). member of the phylum Verrucomicrobia. As a normal
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NAFLD is accompanied by an impaired host immune bacterium in the intestines of humans and animals,
response, and thus, an increased abundance of gut A. muciniphila acts on mucin and uses it as its sole carbon
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A. muciniphila can strengthen the integrity of the gut barrier and nitrogen source. A. muciniphila is normally present
and minimize the leakage of harmful bacterial products in the gut of the human host shortly after birth, peaks
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from the gut to portal vein circulation. Taken together, these shortly after birth, and decreases with age. A. muciniphila
results indicate that the beneficial effects of H on NAFLD can protect the intestinal epithelial cells and maintain
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appear to be associated with increases in the relative the integrity of the mucus layer so that the intestinal
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abundance of gut A. muciniphila and downregulation of the permeability is not damaged. The intestinal barrier
expression of systemic inflammatory factors. ensures nutrient absorption and prevents the escape of
microorganisms and their products. Upon damage to
4. Discussion the intestinal barrier, the harmful products enter the
bloodstream from the lumen and then activate an immune
The liver is the most important metabolic organ for response leading to inflammation. Oral administration
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maintaining normal glucose and lipid homeostasis, and of A. muciniphila increased the expression of intestinal
this status can be deranged by chronic inflammation in tight junction proteins in NAFLD mice. Therefore,
obesity-associated NAFLD. NAFLD initially manifested as A. muciniphila was proposed to reduce endotoxemia levels
liver steatosis and steatohepatitis, and may gradually develop and improve local inflammation by improving intestinal
into more serious diseases such as cirrhosis and liver cancer. permeability and strengthening the intestinal barrier.
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While many previous studies have shown that NAFLD Nutritionally unbalanced diets, such as HFD, can affect the
patients usually gain significantly more weight than normal intestinal microenvironment and reduce the abundance of
individuals, it has since been found that normal-weight and A. muciniphila in the intestine. However, weight loss and
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underweight individuals may also have NAFLD. Low-grade increased insulin sensitivity were found in obese human
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metabolic inflammation is a common feature of NAFLD. volunteers who were given oral 10 A. muciniphila daily.
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10
NAFLD begins with the excessive accumulation of fat in liver The mice treated with A. muciniphila also demonstrated
tissue, which is caused by increased fat intake, deregulation of significantly reduced serum TGs and fasting blood glucose,
lipoprotein synthesis, and insulin resistance. Subsequently, and increased insulin sensitivity. Due to its beneficial role
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oxidative stress induced hepatocyte injury, production of in many diseases, A. muciniphila is expected to be the next
pro-inflammatory factors, mitochondrial damage, and generation of probiotics. 32
intestinal flora disorder. 22
As a colorless, odorless, non-polar, and minimal
The gut and liver can interact through a pathway called molecule in nature, inhaled H can rapidly diffuse through
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the gut-liver axis. More than 50% of the liver’s blood comes alveoli into the blood and penetrate the cell membrane
from the intestine, and the portal vein is the “bridge” system to exert systemic effect. As early as 1975, H was
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between the two tissues. Therefore, the liver is one of the reported to be effective in treating skin cancer in mice.
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most vulnerable organs to enterogenic endotoxin and In addition, the safety of breathing H in humans has
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the “front line” to resist bacterial metabolites. It has been been demonstrated in studies related to diving-related
proposed that intestinal flora can maintain physiological treatments. Recently, H inhalation was reported to
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Volume 1 Issue 2 (2024) 76 doi: 10.36922/mi.3896