Studies have shown that high-fat diets can disturb the natural gut microbiota in a way that allows for the establishment and growth of harmful bacteria, like Bilophila wadsworthia, which occupy the vacant niches left in the gut by a poor diet. As these microbes form colonies, they activate the receptors to produce lipopolysaccharide (LPS), which causes prolonged activation of the immune system. Over time, this deteriorates the gut barrier, which allows bacteria and their products to enter the bloodstream. Once that happens, the body activates a prolonged immune response to fight the constant influx of bacterial matter. If the source of invasion is not remedied or the bacteria are not otherwise eliminated, the immune system will exist in a chronically inflamed state.
As shown in the study by Sokol et al., much of the resulting inflammation is driven by activation of the TLR4 pathway, which is a direct response to the accumulation of LPS. The TLR4 pathway is responsible for later initiating downstream cytokine signaling. When TLR4 is activated by the presence of a pathogen, it increases the production of cytokines TNF-α, IL-6, and IFN-γ. These cytokines will work to remove harmful bacteria from the gut, as well as having an impact on other systemic processes, such as the regulation of blood-glucose levels. In the study presented, mice were exposed to both the high-fat diet and a normal diet, and the mice on a high-fat diet showed increased levels of B. wadsworthia, impaired glucose tolerance, and increased liver fat. This study also reported that using a probiotic to reduce the number of Bilophila wasdworthia led to decreased systemic stress from signaling.
As previously mentioned, a high‑sugar diet can reshape the gut microbiota in ways that cause inflammation. In this experiment, mice that were fed a high sugar diet developed more severe colon inflammation than those on a non-supplemented diet. In particular, the sugar diet promoted the growth of bacteria responsible for the destruction of mucus-producing cells. Some of the common species responsible are Akkermansia muciniphila and Bacteroides fragilis. As mentioned previously, this can lead to exaggerated immun activation due to the epithelium of the gut being exposed to an increased number of pathogens without the protection of mucus. These types of organisms must be eliminated or at least lowered in number so that they cannot produce LPS that damages the gut lining
This study also showed that a high‑sugar diet reduced the population of butyrate-producing bacteria, which are important for maintaining the gut barrier. The resulting decrease in butyrate means increased inflammation of the gut epithelium and the immune system, which weakens the regulation of TLR and NLR signaling pathways. As previously mentioned, lower butyrate levels cause epithelial and myeloid cells to become more exposed and sensitive to particles like LPS. This leads to heightened TLR4 pathway activation, which in turn causes downstream NF-kB signaling. This prepares the NLRP3 inflammasome for release by macrophages or dendritic cells, promoting IL‑1B production, which leads to inflammation. This study does a good job of showing how a high-sugar diet can cause multiple problems that exacerbate each other unless the source of dysbiosis is addressed.
Dietary fiber, as described in this study, is used in the process of fermentation by gut microbiota to produce short-chain fatty acids (SCFAs). These cell products are crucial for controlling immune processes. SCFAs act through multiple mechanisms to alter the gene products of cells in the immune system, nervous system, and intestines. Butyrate and other SCFAs promote the production of regulatory T cells (Tregs) and increase the secretion of anti-inflammatory cytokine IL‑10. SCFAs also support antigen-presenting cells and macrophages, which in turn reduces their output of pro‑inflammatory cytokines like IL-6 and TNF‑a.
As suggested by the studies above, increasing dietary fiber can help correct dysbiosis by promoting the growth of normal bacteria in the gut. This will lead to the establishment of SCFA-producing bacteria. The return of these organisms to normal levels and the influx of available SCFAs will allow for repair of the intestinal barrier and decreased inflammation. A high-fiber diet supports Treg production and activity, as well as anti-inflammatory cytokine production. The studies above all imply that shifting from a low-fiber, high-fat/sugar to a high-fiber, low-fat/sugar diet can reverse microbial imbalances and help to support the recovery of damaged cells.
Microbiology 251 Blog 