In a recent study published in Infectious Medicine, researchers assessed the role of the gut microbiome in human health and disease.

Background

Microbiota is the aggregate of bacteria, fungi, and other microorganisms found on or within humans, and the genes that microbiota carry create the microbiome. The immense technological advances and diversity of knowledge that have occurred in recent years have aided in the progress of microbiome research, supporting our understanding of the microbiome and its relevance to human health.

Gut microbiota and human diseases

The human microbiome has been shown to be an important component of human health. Dysbiosis is a condition in which unique alterations occur in the human microbiome.

Cancer

The gut microbiota is considered to be responsible for 20% of all cancer incidences worldwide. According to research, F. nucleatum suppresses the host immunological response and stimulates cellular growth. Butyrate is an essential ingredient for a healthy colon. Butyrate-producing genera were essentially non-existent in the feces of colorectal cancer patients. Bacteria such as Acidaminobacter, Phascolarctobacterium, and Citrobacter were found in considerable numbers in the stool samples of colorectal cancer (CRC) patients.

Many studies have been conducted, and two major hypotheses exist to imply an association between cancer and dysbiosis. The alpha drug hypothesis proposes that the presence of enterotoxigenic bacterial species Bacteroides fragilis disturbs the colonic microbiota, triggering inflammatory responses such as cytokines such as interleukin-17 (IL-17), tumor necrosis factor (TNF-α), and T-helper-17 (TH17), which promotes cancer growth.

In another hypothesis model known as the bacterial driver-passenger driver, bacteria Bacteroides fragilis results in inflammation. As a result of this inflammation response, genotoxins are produced, causing cell proliferation and some serious mutations that lead to adenoma formation.

Inflammatory bowel disease (IBD)

Irritable bowel syndrome is a kind of inflammatory bowel disease that impacts people with IBD. Ulcerative colitis (UC) only affects the colon. Lactobacilli species were less abundant during the active phase of disease, while several species, such as Lactobacillus salivarus, Lactobacillus manihotivorans, and Pediococcus acidilactici, were detected during the remission period rather than during the active phase.

According to studies, increased E. coli loads are associated with pathology and the development of colitis. Roseburia hominis and Faecalibacterium prausnitzii were found in small amounts in UC patients' feces. Bacterial families such as Lachnospiraceae and Ruminococcaceae were also present in lower numbers.

Metabolic disorders

Obesity

Eating habits have a significant impact on gut microbial makeup. The gut microbiome is altered as a result of a high-fat diet, with higher quantities of Firmicutes and Proteobacteria and lower levels of Bacteroidetes. Firmicutes to Bacteroides ratio has been associated with body weight, with obese people having a higher ratio. Clostridium difficile infections can potentially induce obesity.

Obesity is influenced by a chronic inflammatory state caused by gut bacteria or metabolites that modulate the microbiota-brain-gut axis. Bariatric surgery is a popular therapeutic option for severe obesity. Weight loss during bariatric surgery is likewise associated with an increase in the abundance of B. thetaiotaomicron and a reduction in serum glutamate levels.

Liver disease

The gut absorbs beneficial chemicals produced by the liver. The intestinal microbiota produces ammonia, ethanol, and acetaldehyde, which the liver metabolizes, thus regulating cytokine production and Kupffer cell activity. When antibiotics inhibit gut flora, the severity of Concanavalin-A (ConA)-induced hepatitis increases. In investigations, intestinal bacteria that create hydrogen have been demonstrated to diminish ConA-induced inflammation. Liver damage caused by excessive alcohol use is also linked to gut microbiota dysbiosis. Additionally, the synthesis of ammonia from amino acids by some urease-positive bacteria is a significant element in the pathophysiology of hepatic encephalopathy (HE).

Cardiovascular diseases

Atherosclerosis, heart failure, and hypertension are all examples of cardiovascular diseases. The detection of Enterobacteriaceae and Streptococcus spp. in the gut microbiome is associated with atherosclerotic cardiovascular disease (ACVD). Bacteroides, Clostridium, and Lactobacillales are believed to be diagnostic markers in coronary artery disease patients.

The use of Bifidobacterium animalis subsp. lactis LKM512 as a probiotic has demonstrated lowered trimethylamine (TMA) levels and particular bacterial groups such as Clostridia, Clostridiales, and Lachnospiraceae that produce TMA, reducing the risk of arteriosclerosis.

Human immunodeficiency virus (HIV)

CD4+ T cells are essential for early HIV replication. The human gastrointestinal (GI) tract is a reservoir for these cells, making the GI tract a reservoir for acquired immunodeficiency syndrome (AIDS). AIDS from HIV infection is caused by chronic systemic inflammation, translocation of immunological stimulatory microbial products, and disruption of the intestinal immune barrier. Viremic untreated (VU) HIV-infected patients were compared to HIV subject samples. It was discovered that Erysipelotrichaceae in the class Mollicutes, which is responsible for obesity and cardiovascular morbidity, is the most common pathogen found in VU subjects, as well as pro-inflammatory pathogens from the Enterobacteriaceae family.

Conclusion

Overall, the study findings showed that diseases caused by disruptions in the natural microbiota composition include gastrointestinal, metabolic, immunological regulatory, and neurodevelopmental disorders. Gut microbial equilibrium should be maintained for overall health. More research is needed to identify these metabolite-producing gut bacteria for potential medicinal applications.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.