Gut Bacterial and Fungal Dysbiosis in Patients with Non-Statutory Infectious Diarrhea in Hohhot: A 16S rRNA and ITS Amplicon Sequencing Case–Control Study

Inside the human gut, a vast and bustling community of microscopic life works tirelessly to keep the body healthy. This ecosystem is not a single monolith but a complex society made up of two distinct groups: bacteria and fungi. While bacteria have long been recognized as the primary residents, fungi also play a crucial role, and the two groups constantly interact, competing for space and resources while helping to digest food and train the immune system. When this delicate balance is disturbed, a state known as dysbiosis occurs, often leading to illness. One common and widespread illness in China is non-statutory infectious diarrhea, a condition caused by various germs that leads to frequent, loose, or watery stools. Unlike severe, notifiable diseases such as cholera, these cases are often less dramatic individually but collectively represent a massive public health challenge. Understanding exactly how the gut's microbial community changes during these infections is essential for developing better treatments, yet scientists have historically struggled to see the full picture because they often studied bacteria and fungi separately, missing the complex ways they influence one another.

A team of researchers in Hohhot, Inner Mongolia, decided to look at this problem with a fresh perspective by examining both bacterial and fungal communities at the same time. They collected stool samples from 85 patients suffering from infectious diarrhea and compared them with samples from 70 healthy people. Using advanced genetic sequencing techniques, the scientists were able to read the unique DNA signatures of the microbes present in each sample, allowing them to identify exactly which species were there and in what numbers. This approach provided a detailed map of the gut's internal landscape, revealing how the community structure shifts when a person becomes sick. The study focused on a specific region of the gut microbiome that had not been thoroughly explored in this context, aiming to find specific microbial patterns that could serve as warning signs or targets for therapy.

The investigation revealed that infectious diarrhea causes a profound disruption to the gut's ecosystem, but the impact is not felt equally by all residents. The bacterial community suffered the most severe damage. In healthy individuals, the gut is home to a rich variety of bacteria, including many that produce beneficial compounds to keep the intestinal lining strong. In the patients, this diversity collapsed. The researchers found that the number of different bacterial species dropped significantly, and the overall balance of the community was thrown into chaos. Specifically, the bacteria that are known to be helpful, such as those that produce butyrate—a vital fuel for the cells lining the colon—were nearly wiped out. In their place, opportunistic bacteria that can cause harm began to multiply rapidly. These include types of Escherichia and Streptococcus, which are often associated with infection and inflammation. The fungal community also changed, but the shift was less dramatic. While the total number of fungal species decreased, the overall structure of the fungal network remained more stable than the bacterial one. However, the patients did show a significant increase in Candida, a type of fungus that can become problematic when the body's defenses are down, alongside a decrease in Aspergillus.

One of the most striking discoveries in this study was how age shapes these microbial changes. The researchers found that the gut microbiome does not react to illness in the same way for a baby as it does for an elderly person. In the bacterial world, diversity follows a clear life cycle: it is lowest in infants, rises to a peak during adulthood, and then declines again in older age. When the patients became sick, this age-dependent pattern was preserved but distorted. Infants showed a very different microbial profile compared to adults, dominated by bacteria that are typical for their developmental stage, while older adults showed a distinct loss of protective bacteria and a rise in harmful ones. The fungal community, however, did not show such strong age-related structural changes; instead, the main difference across ages was simply the number of different fungal species present. This suggests that while the bacterial community is deeply woven into the host's biological development, the fungal community is more influenced by external factors like diet and environment, maintaining a more consistent structure regardless of the patient's age.

The study also tested whether these microbial changes could be used to diagnose the illness. By using a computer model to analyze the data, the researchers found that the presence or absence of just three specific bacterial genera—Faecalibacterium, Roseburia, and Ruminococcus—could identify a patient with a very high degree of accuracy. These are all bacteria that produce butyrate, and their severe depletion in sick patients makes them excellent markers for the disease. In contrast, the fungal markers were not as reliable for diagnosis, reinforcing the idea that the bacterial community is the primary driver of the visible changes during an infection. The researchers noted that their findings are specific to the population in Hohhot and that the study design, which looked at a single point in time, shows a strong association between the microbial changes and the illness but does not prove that the changes caused the disease. Nevertheless, the work provides a clear baseline for understanding how the gut ecosystem collapses during infectious diarrhea, highlighting that the loss of beneficial bacteria is a central feature of the illness and that age is a critical factor in how the body's internal world responds to infection.