Experiments for studying effects of bacteria on treating health problems and promoting good health have been performed for a long time. Theodor Escherich has been credited as the first pediatric infectious disease physician and described Bacterium coli commune (now referred to as Escherichia coli) in 1886 ^[1][9]. While working under Theodor Escherich, Dr. Józef Brudziński treated infants for acute infectious diarrhea by using a Bacillus lactis aërogenes suspension described in publications from 1899 ^[2][3][10,11]. Although Élie Metchnikoff ^[4][12] believed that intestinal putrefaction can shorten life, he noted the work of Dr. Brudziński and similar work by Dr. Henry Tissier and recommended people “to absorb large quantities of microbes”. He believed that lactic bacteria can fight against intestinal putrefaction. He also wrote that Stamen Grigoroff observed many centenarians in Bulgaria, which is a region where yahourth (yogurt) was commonly consumed ^[4][12]. The fact that diet affects the types of bacteria that develops within the intestinal tract was first clearly established by Herter and Kendall in 1910, but suggested as early as 1886 by Escherich and Hirschler ^[5][13].

Many of the starter cultures and probiotics now used in yogurt making were first described in the late 1800s or early 1900s. The name “Streptococcos” was first used in 1874 by Albert Theodor Billroth ^[6][14]. Streptococcus thermophilus (later reclassified as Streptococcus salivarius subsp. thermophilus by Farrow and Collins in 1984 ^[7][15] but revived back to Streptococcus thermophilus by Schleifer et al. in 1991 ^[8][16]) was described by S. Orla-Jensen in 1919 ^[9][17]. In 1901, Martinus Beijerinck proposed the genus Lactobacillus to include Gram-positive, fermentative, facultatively anaerobic, non-sporeforming bacteria ^[10][18]. Stamen Grigoroff discovered Bulgarian bacillus (now Lactobacillus delbrueckii ssp. bulgaricus) in 1905 ^[11][19]. Lactobacillus acidophilus (originally called Bacillus acidophilus) was described by Ernst Moro in 1900 ^[12][20]. In 1899 and 1900, Henry Tissier first described Bacillus bifidus communis, later referred to as Lactobacillus bifidus and now referred to as Bifidobacterium ^[13][21]. He found that Bifidobacteria was the main type of bacteria comprising the gut microflora of breast-fed babies and Bifidobacteria could treat acute gastroenteritis ^[11][19].

Dr. Isaac Carosso recommended to his patients who suffered from gastrointestinal problems to consume yogurt. Afterwards, he started producing yogurt and founded the Danone Company in 1919 ^[11][19].

The term “probiotic” (meaning “for life”) originated in 1953 from Werner Kollath to mean “active substances that are essential for a healthy development of life” ^[14][22]. Lilly and Stillwell ^[15][23] used the term probiotic as “substances secreted by one organism which stimulate the growth of another” in 1965. Parker ^[16][24] described probiotics as “organisms and substances which contribute to intestinal microbial balance” in 1974. Fuller ^[17][25] defined probiotics as “A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance” in 1989. A panel from the International Scientific Association for Probiotics and Prebiotics defined probiotic as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” in 2014 ^[18][26].

2. 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 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 Gram-positive and are involved in short chain fatty acid synthesis and in hunger and satiety regulation ^[19][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 ^[19][113]. The Firmicutes phylum includes Clostridium (95% of this phylum), Lactobacillus, Bacillus, Enterococcus, and Ruminicoccus genera, and the Bacteroidetes phylum consists of Bacteroides and Prevotella genera ^[20][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 ^[21][115]. The microbiome produces a wide variety of metabolites and can account for some of the variation in plasma metabolites between individuals ^[22][116]. The composition of the gut microbiome and gut-derived metabolites are associated with the occurrence of a wide variety of chronic diseases ^[23][117]. In addition, the effect that diet and exercise have on cognition is affected by the gut microbiome ^[24][118]. Furthermore, the microbiota was found to affect social behavior in zebrafish during early neurodevelopment ^[25][119]. However, the gut microflora can be affected by various factors including consumption of fermented dairy products ^[26][27][28][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 ^[29][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 ^[30][124]. Probiotics provide many health benefits. Some of these health benefits provided by probiotics, postbiotics, and paraprobiotics (to be discussed later) with either mixed or strong evidence for effectiveness in clinical trials are summarized in Table 13 ^{[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131]}[125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,148,149,150,151,152,153,154,155,156,157,158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179,180,181,182,183,184,185,186,187,188,189,190,191,192,193,194,195,196,197,198,199,200,201,202,203,204,205,206,207,208,209,210,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225]. Because of the complexity involved in being consistent when evaluating the strength of the evidence for the effectiveness of probiotics in preventing or treating each of these adverse health conditions or providing the health benefits, no attempt was made for this evaluation. The efficacy of probiotics in controlling Crohn’s disease usually could not be shown ^[132][226]. More details about the health benefits provided by yogurt and probiotic fermented milks are provided by Sakandar and Zhang ^[133][227], and Hadjimbei et al. ^[134][228].