## 4 Gut Microbiome, Inflammation, and Health Benefits Provided by Probiotics  
The human gut microbiome (also known as microbiota or microflora) consists of bacteria (predominantly obligate anaerobes), archaea, fungi, and protists and functions \begin{table}
\begin{tabular}{c l l l l} \hline \hline
**GRN Number** & **Substance (Beneficial Microorganism)** & **Notifier** & **Status 1** & **Date of Closure** \\ \hline
377 & _Bifidobacterium animalis subsp. lactis_ & Cargill, Inc. & No questions & 9/29/2011 \\  & strain Bf-6 & & & \\
357 & _Lactobacillus acidophilus_ NCFM & Danisco USA, Inc. & No questions & 4/19/2011 \\
288 & _Lactobacillus rhamnus_ strain HN001 & Fonterra Co-operative Group & No questions & 11/1/2009 \\  & & Morinaga Milk Industry & No questions & 7/8/2009 \\
268 & _Bifidobacterium longum_ strain BB536 & Co., Ltd. & No questions & 7/8/2009 \\
254 & _Lactobacillus reuteri_ strain DSM 17938 & BioGaia AB & No questions & 5/29/2008 \\ \hline \hline \end{tabular}  
* 1
* No questions” means “FDA has no questions”. 2 Some uses may require a color additive petition.  
\end{table} 
Table 2: Cont. by metabolizing nutrients (by converting indigestible carbohydrates into short-chain fatty acids) for the host, maintaining the gut mucosal barrier, modifying the immune system, inhibiting pathogens, and even affecting brain activities. Most of these bacteria belong to the Firmicutes and Bacteroidetes phyla with fewer bacteria belonging to Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia phyla. Firmicutes bacteria are Grampositive and are involved in short chain fatty acid synthesis and in hunger and satiety regulation [113]. Bacteroidetes bacteria are Gram-negative and are involved with enhancing immune reactions and inflammation. A loss of a balanced ratio between Firmicutes and Bacteroidetes leads to dysbiosis (lack of normal intestinal homeostasis), obesity (increased Firmicutes to Bacteroidetes ratio), inflammatory bowel disease (decreased Firmicutes to Bacteroidetes ratio), and other diseases [113]. The Firmicutes phylum includes _Clostidium_ (95% of this phylum), _Lactobacillus_, _Bacillus_, _Enterococcus_, and _Ruminicoccus_ genera, and the Bacteroidetes phylum consists of _Bacteroides_ and _Prevotella_ genera [114]. Although early studies estimated the microorganism population as more than 100 trillion and number of human cells as around 10 trillion, more recent estimates state a ratio of 1.3 bacteria cells to each human cell [115]. The microbiome produces a wide variety of metabolites and can account for some of the variation in plasma metabolites between individuals [116]. The composition of the gut microbiome and gut-derived metabolites are associated with the occurrence of a wide variety of chronic diseases [117]. In addition, the effect that diet and exercise have on cognition is affected by the gut microbiome [118]. Furthermore, the microbiota was found to affect social behavior in zebrafish during early neurodevelop [119]. However, the gut microflora can be affected by various factors including consumption of fermented dairy products [120, 121, 122]. While acute (high-grade but short-term) inflammation is needed for healing, trigger removal, and tissue repair, systemic chronic (low-grade but persistent) inflammation can lead to a wide variety of adverse health conditions including metabolic syndrome (hypertension, hyperglycemia, and dyslipidemia), type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular disease, chronic kidney disease, multiple cancer types, depression, neurodegenerative and autoimmune diseases, osteoporosis, and sarcopenia [123]. Probiotics, along with prebiotics, resistant starch, and resistant proteins, can decrease chronic low-grade inflammation by producing short-chain fatty acids (acetate, propionate, and butyrate), improving phagocytic activity, and reducing pro-inflammatory cytokine production to potentially promote healthy aging [124]. Probiotics provide many health benefits.