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Other inflammatory or autoimmune conditions

Allergy, asthma, and diabetes mellitus type 1 are autoimmune and inflammatory disorders' the causes of these disease are unknown and issues with the gut flora and its relationship with the host have been implicated in these conditions.

 Two hypotheses have been posed to explain the rising prevalence of these diseases in the developed world: the hygiene hypothesis, which posits that children in the developed world are not exposed to a wide enough range of pathogens and end up with an overreactive immune system, and the role of the Western pattern diet which lacks whole grains and fiber and has an overabundance of simple sugars. Both hypotheses converge on the changes in the gut flora and its role in modulating the immune system, and as of 2016 this was an active area of research.

Similar hypotheses have been posited for the rise of food and other allergies. The theory of dysbiotic drift intersects the current hypotheses and proposes that individuals in modernized societies suffer a form of microbiome dysbiosis caused by reduced intensity and reduced diversity of microbial exposure. This form of dysbiosis is associated with an increased prevalence of allergies.

Food allergy results from failed immune tolerance of food. An immune response to food antigens is directed by T helper type-2 (TH2) cells, IL-4 and IgE antibodies. Conversely, tolerance of food involves an immune response that is mediated by T regulatory cells and IL-10 which suppress allergy-promoting TH2 cells and IgE. Evidence for the role of diminished gut microbiota in food allergies is demonstrated in mouse models. Reconstitution of germ-free mice with a defined mix of normal bacterial strains (Altered Schaedler Flora containing 2 Lactobacillus species, a Bacteroides species, a spiral bacterium of the Flexistipes genus and 4 Fusobacterium species) induces intestinal T regulatory cells and IL-10 responses that prevent the formation of experimental food allergy. The mechanisms of inducing the tolerance-inducing immune responses are complex and not well-understood.

As of 2016 it was not clear if changes to the gut flora cause these auto-immune and inflammatory disorders or are a product of them or adaptation to them.

Accumulated data from randomized, placebo-controlled clinical trials in humans is too uncertain and heterogenous to prove conclusively whether the use of probiotics or prebiotics can prevent food allergies or eczema. More standardized studies are needed to assess beneficial effects of shaping microbiota to prevent food allergy or before practical recommendations on specific bacterial strains, optimal doses and treatment timing can be made.  As of 2017, probiotic and prebiotic supplements for allergy prevention are not generally recommended by international expert bodies including the American Association of Pediatrics, European Society for Pediatric Gastroenterology Hepatology and Nutrition, and the Food and Agriculture Organization of the United Nations/ World Health Organization.