Gut-Immune Interactions

The basic idea

Microbes in the gut provide signals that the immune system uses to develop and work properly, and the relationship runs both ways. A review in Nature Reviews Immunology says the microbiota provides crucial signals for development and function of the immune system and influences susceptibility to many immune-mediated diseases. [1] Researchers also study the chemical products of microbes (metabolites), such as short-chain fatty acids, which affect T cells, B cells and other immune cells. [2][3] See Microbial Metabolites and Short-Chain Fatty Acids.

Evidence labels: approved medicine, established, promising but limited, mixed, insufficient evidence, preclinical (cells/animals only). Immune marker changes are not infection prevention.

What differences in people mean

Changes in gut microbes and their metabolites have been recognized in many immune-related inflammatory disorders, including inflammatory bowel disease, diabetes, rheumatoid arthritis and lupus. [2] Label: association. Whether the change causes the disease, results from it, or comes from diet and medicines is mostly unresolved. See Microbiome Studies: Association vs Causation.

Trials of microbiota-based therapies in autoimmune disease

A 2024 meta-analysis pooled 80 randomized trials of gut microbiota-based therapies (the search was for probiotics) across 14 autoimmune conditions. It reported possible improvement in symptoms or inflammation markers for several, such as psoriasis, multiple sclerosis, lupus, Crohn's disease and ulcerative colitis, but not for spondyloarthritis or rheumatoid arthritis, and no increase in adverse events. [4]

Label: mixed. The review covered many different products, conditions and outcomes, so it cannot say that any particular product works for a particular person. Marker changes are not the same as fewer flares. Product specifics are in Probiotic Supplements Explained.

Gut microbes and cancer immunotherapy

A multicenter phase I trial gave stool-derived material from healthy donors, a procedure called fecal microbiota transplantation (FMT), together with a PD-1 inhibitor (an immune checkpoint drug) to 20 previously untreated people with advanced melanoma. The main aim was safety. No grade 3 adverse events were reported from the FMT alone, and 5 patients (25%) had grade 3 immune-related adverse events from the combination. The objective response rate was 65% (13 of 20). [5]

Label: investigational; promising but limited. There was no comparison group, and a response rate in a single small trial cannot be compared with approved treatment. A correction (erratum) to this paper was published. [5] FMT is a clinical procedure done only in trials or approved settings; see Fecal Microbiota-Based Therapies for what is approved and what is not. Do not attempt it at home.

Risks to know about

• Probiotics are not risk-free. The FDA has warned that premature infants given probiotics are at risk of severe, potentially fatal infections from the organisms in the products. [6]
• People with weakened immune systems should ask their clinician first. NCCIH notes that, in trials where probiotics were given along with antibiotics to prevent diarrhea, use appeared safe except in patients who are very weak or have poorly functioning immune systems. [6]
• A claim that a gut product strengthens immunity against infections is a marketing claim unless a trial measured infections. For more, see Laboratory Immune Effects vs Clinical Benefit.

How to evaluate claims

• Did the study measure illness, symptoms or only a blood marker?
• Which product and strain were tested, in which condition?
• Was there a placebo group?