In a nationwide study in Finland: Oral antibiotics can significantly increase the risk of Parkinson’s disease, be careful! Antibiotics can also increase the risk of mental illness and whether a child is smart or not, who has the final say. Food and Mind introduced that antibiotic use may increase the risk of children’s neurodevelopmental disorders, elderly neurodegenerative problems, and mental illness. Food and Mind has mainly focused on studying depression and anxiety disorders in the past. This issue introduces some new studies on depression.
I. The more antibiotics used, the higher the risk of depression
Recently, a retrospective cohort study in South Korea (nationwide, involving nearly 200,000 adults) found a dose-dependent relationship between antibiotic exposure and depression incidence. The longer the cumulative antibiotic exposure days, the higher the risk of depression. A broader spectrum of antibiotics is associated with a higher risk of depression. (Antibiotic exposure and depression incidence: A cohort study of the Korean population – ScienceDirect)
A systematic review in January 2023 also found a potential association between antibiotic exposure and subsequent development of depressive symptoms. Specifically, studies from the UK and Sweden suggest that the risk of depression increases by at least 20% after antibiotic exposure. The former (involving over 1 million participants) reported that the risk remains and slowly declines over the following decade after increasing the duration of use and the number of drugs. (Antibiotic use and the development of depression: A systematic review – ScienceDirect)
In other words, the threat of antibiotics to the risk of depression persists for up to ten years after treatment. This effect may be related to the lasting changes in intestinal barrier function caused by antibiotics.
II. Antibiotics impair intestinal barrier function
Article: A history of repeated antibiotic usage leads to microbiota-dependent mucus defects
Journal: Gut Microbes
Date: July 2024
Researchers selected 8 participants from 2509 Estonian adults who had not used antibiotics in the six months before fecal sampling. Four individuals had undergone at least 5 courses of antibiotics in the past 5 years and were categorized as the antibiotic treatment group (with a history of multiple antibiotic treatments); four individuals had not used antibiotics in the past 10 years and served as the control group. Both groups of participants were physically healthy, had a normal BMI, had no history of complex diseases or recent medication use, and were matched for gender, age, stool form, and diet.
Microbiota analysis showed that compared to the control group, the antibiotic treatment group had significantly reduced intestinal microbial diversity and richness. There were changes in the abundance of genera such as Bacteroides, Lachnospira, Ruminococcus, Blautia, Clostridium, and Akkermansia.
Researchers transplanted the microbiota of these two groups into germ-free adult mice. Results showed that there was no difference in colonic mucin thickness between the two groups, and neither group showed significant intestinal inflammation. However, mice that received the antibiotic treatment group microbiota exhibited a significant decrease in colonic mucin growth rate, with more microorganisms distributed in the mucus layer (closer to the epithelial cells) and fewer goblet cells (responsible for mucin secretion). Although the expression levels of mucin Muc2 and antimicrobial lectin Reg3γ significantly increased, this compensatory response did not repair the mucin function defects.
Metabolomics analysis revealed that although the total weight was similar, mice that received the antibiotic treatment group microbiota had more abdominal fat, with a significant increase in the percentage of abdominal fat relative to total weight (indicating increased visceral fat, central obesity) compared to mice that received the control group microbiota.
Metagenomic analysis confirmed that the human fecal microbiota of these two groups were successfully transplanted into the mice. Mice that received the antibiotic treatment group microbiota had a significantly increased abundance of microbes in the gut that can degrade mucin proteins, such as Akkermansia muciniphila, Blautia producta, Parasutterella excrementihominis, Bacteroides fragilis, and Bacteroides salyersiae, compared to mice that received the control group microbiota.
Metabolomics analysis indicated that compared to the mice that received the control group microbiota, mice that received the antibiotic treatment group microbiota were enriched in adenine, adenosine, betaine, butyl esters, 4-hydroxybenzoic acid esters, dihydroxybenzoic acid esters, 4-imidazoleacetic acid, propyl esters, and valeryl esters.
This study suggests that in addition to disrupting the microbiota, experiencing multiple antibiotic treatments can weaken the intestinal mucus barrier. Even though individuals seem to have recovered their health after antibiotic treatment and show no abnormal indicators of disease or inflammation, mucosal layer function damage still exists. Although the gut microbiota and host mucosal layer are in dynamic balance, the erosion of mucin-enriching bacteria and mucin function damage caused by antibiotics may increase the risk of infection and obesity.
Food and Mind’s gentle conclusion: Several years ago, Food and Mind pointed out that abnormal intestinal flora and the associated gut-brain-axis disorder are the main pathological basis of depression, disrupting the flora can increase the risk of depression, while protecting the flora can reduce the risk of depression and even treat depression.
There is increasing evidence in this area of research. Besides antibiotics, factors such as life stress, poor diet, and unhealthy lifestyles can disrupt the intestinal flora, triggering depression. Although the impact of these factors may initially be small, similar to the intestinal mucin functional damage caused by antibiotics, which often occurs unnoticed by individuals, slight adjustments to diet can restore it. However, the cumulative effects of long-term accumulation and various factors are often overwhelming.
In daily life, people often attribute stressful life events as triggers for depression, as the final straw that breaks the camel’s back, and spend a lot of effort and money to remedy this. However, other factors should not be overlooked. Only by simultaneously controlling these factors can depression be better treated.
In reality, many people have already improved or resolved depression through flora adjustment and dietary control. Dietary interventions for depression, adolescents, and pregnant women need to know: Can you overcome depression by eating?.
However, Food and Mind’s readers are often more intelligent; they consciously adjust their flora after experiencing high stress, staying up late, or having to use antibiotics, such as supplementing probiotics/prebiotics, consuming high-fiber legumes and grains, increasing exercise, and other methods to restore healthy flora. It is better to mend the pen after the sheep are lost, actively repair after the destruction of the intestinal flora, nip the bud of depression early, and avoid the occurrence of severe infections or psychological problems.
