The impact of dietary fiber and probiotics in infectious diseases

Journal Pre-proof The impact of dietary fiber and probiotics in infectious diseases Huan Yang, Yiran Sun, Rui Cai, Ying Chen, Bing Gu PII:

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https://doi.org/10.1016/j.micpath.2019.103931

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YMPAT 103931

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Microbial Pathogenesis

Received Date: 1 September 2019 Revised Date:

10 December 2019

Accepted Date: 14 December 2019

Please cite this article as: Yang H, Sun Y, Cai R, Chen Y, Gu B, The impact of dietary fiber and probiotics in infectious diseases, Microbial Pathogenesis (2020), doi: https://doi.org/10.1016/ j.micpath.2019.103931. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.

1

The Impact of Dietary Fiber and Probiotics in Infectious Diseases

2

Huan Yang1#, Yiran Sun2#, Rui Cai1, Ying Chen1, Bing Gu1*

3 4

Author affiliation:

5

1

Medical Technology School of Xuzhou Medical University, Xuzhou 221004, China

6

2

Clinical School of Xuzhou Medical University, Xuzhou 221004, China

7

*Correspondence Author: Bing Gu, Department of Laboratory Medicine, Affiliated

8

Hospital of Xuzhou Medical University, Xuzhou 221006, China E-mail:

9

[email protected].

10

#Authors share co-first authorship.

11

Acknowledgement

12

This research was supported by the National Natural Science Foundation of China

13

(81871734), Jiangsu Privincial Medical Talent (ZDRCA2016053), Six talent peaks

14

project of Jiangsu Province (WSN-135), Advanced health talent of six-one project of

15

Jiangsu Province (LGY2016042).

16

Abstract

17

Although antibiotics are commonly used to treat infectious diseases, emergence of

18

antibiotic resistant strains highlights the necessity for developing novel alternative

19

approaches. Meanwhile, clinically, antibiotics can destroy the gut microbes balance,

20

which is not conducive to the recovery of infectious disorders. As a result, recent

21

studies have begun to explore potential prevention and treatment methods for

22

infectious diseases, starting with more readily available dietary fiber and probiotics.

23

Moreover, researches have shown the personalized nature of host responses to dietary

24

fiber intervention, with outcomes being dependent on individual pre-treatment gut

25

microbes. In this review, we will focus on the roles of dietary fiber and probiotics on

26

infectious diseases, how probiotics and dietary fiber work on infectious diseases and

27

then explore their mechanisms, so as to guide clinical consideration of new therapies

28

for infectious diseases.

29

Keywords: dietary fiber; probiotics; infectious diseases; gut microbes 1

30

Introduction

31

Following birth, we are colonized with microbes such as archaea, bacteria, fungi,

32

viruses and microeukaryotes [1-3]. The microflora that inhabit the human body provide

33

essential functions for maintaining homoeostasis. In addition to the aforementioned

34

roles for the microbiota, we will focus on an additional function: the ability to

35

influence susceptibility to and outcomes of infectious diseases. Infectious diseases

36

have been considered as a common disease for a long time so that need to be solved

37

clinically. Infections are recognized as playing a critical role in the risk of psychiatric

38

disorders and suicidal behavior. The clinical treatment for infectious diseases has

39

always been the use of antibiotics. However, most studies to date feel that antibiotic

40

treatment do not meet this goal, it has now been found that the abuse of antibiotics

41

interferes with normal medical activities and causes many adverse reactions

42

Hospital-treated and less severe infections treated with antibiotics are associated with

43

the risk of subsequent anorexia nervosa, bulimia nervosa, and eating disorders

44

addition, bacterial resistance is becoming more common, so there has been

45

considerable focus on new therapeutics for highly resistant infections, particularly

46

extensively drug-resistant Gram-negative pathogens [6].

[5]

[4]

.

. In

47

With interest growing in natural therapies, the popularity of probiotics and dietary

48

fiber are on the rise. Many reports showed that dietary fiber and probiotics were

49

closely related to infectious diseases. Higher intake of fiber, especially cereal fiber,

50

has been linked to improving insulin sensitivity, lipid profile, endothelial function,

51

and reducing inflammation. In previous reports, dietary fiber and probiotics may have

52

a role in reducing the fitness of C. difficile in the gut

53

diet supplemented with 10% xylooligosaccharides (XOS), galactooligosaccharides

54

(GOS), inulin, apple pectin or polydextrose that promoted Listeria infection. There

55

are no question of their importance in infectious diseases, however, the efficacy of

56

probiotics and dietary fiber has been controversial. The main controversy of the role

57

of probiotics is the individual differences in the colonization ability. Therefore, the

58

efficacy of probiotics cannot be based solely on animal experiments. Large-scale 2

[7,8]

. While animals were fed a

59

clinical trials are a relatively reliable method. The core probiotics were clinically

60

tested and found to assist in constipation diarrhea, polycystic ovary syndrome, stress

61

and anxiety, ulcerative colitis, inflammatory bowel disease, type 2 diabetes, breast

62

cancer and metabolic syndrome by regulating gut microbiota

63

probiotic and dietary fiber products have been widely used and worth exploring.

[9]

. In summary, the

64

Despite the promising evidence, the role of probiotics and dietary fiber in human

65

health as well as the safety of their application should be further investigated as the

66

current knowledge of the characteristics that are necessary for their function in the

67

infectious diseases is not complete. Besides, due to the complexity of dietary fiber

68

and the diversity of probiotics, the mechanism of their interaction with infectious

69

diseases is unclear. There have been reports that dietary fiber and probiotics can

70

prevent and treat infectious diseases with specific bacterial products such as SCFAs,

71

but other studies have taken a different view. Accordingly, here we will focus on the

72

role and mechanism of dietary fiber and probiotics in infectious diseases. Finally, our

73

aim is to present a modern scientific perspective on dietary fiber and probiotics, then

74

encourage doctors to reconsider new treatments for infectious diseases.

75

Dietary fiber and probiotics are closely related to human health,

76

especially infectious diseases

77

Probiotics are defined by the world health organization (WHO) and the food and

78

agriculture organization (FAO) as microorganisms that, if given in sufficient

79

quantities, will bring health and living organisms to the host

80

used as probiotics belong to genera Lactobacillus, Streptococcus, Bifidobacterium and

81

yeasts [11], in particular Lactic Acid Bacteria (LAB), including the genus Lactobacillus,

82

are the most widely used. It is known that dietary fiber and probiotics can prevent

83

cardiovascular disease, diabetes and other metabolic diseases by improving obesity

84

[12]

85

through immune metabolism, SCFAs, and improving intestinal flora

86

literatures are now extensive, and sometimes there are controversies but there is no

87

question that they are potential and important. Probiotics can be used to correct the

[10]

. Strains most widely

. Probiotics have a positive effect on the prevention and treatment of cancer or

3

[13]

. The

88

antibiotics-induced dysbiosis in critically ill patients. Research on infectious diseases

89

mainly focuses on non-native microorganisms, i.e. pathogens

90

of infectious disease. The effects of probiotics on intestinal and fecal microbiota have

91

been extensively studied, however, there are few studies on the effects of probiotics

92

on the upper respiratory system. A recent systematic review found a favorable

93

outcome of the use of probiotics in reducing the episodes of new respiratory infection

94

in children

95

antibiotic-associated diarrhea and C. difficile infection. A study of 39 randomized

96

clinical trials (9955 patients) analyzed the effects of probiotics on CDI prevention,

97

showing that probiotics prevent C. difficile infection

98

inhibited in presence of L. casei and B. breve. Meanwhile, probiotics have been used

99

to treat Salmonella and Yersinia infection

[15]

[14]

, which are the heart

. Current research reveals that the main indications for probiotics are

[17,18]

[16]

. C. difficile was shown more

. Besides, L. casei showed better

100

effects than the probiotic mixture in inhibiting Salmonella. The selection of antibiotics,

101

probiotics and fecal microflora transplantation seems to be able to regulate the

102

intestinal microflora therapeutically

103

flora, but also in oral and vaginal flora. Oral treatment with Lactobacillus luteus

104

reduced the number of periodontal pathogens in the subgingival microbes

105

Existing studies have made the relationship between probiotics and human health, but

106

the role of probiotics in infectious diseases is still controversial. Probiotic colonization

107

ability has host specificity, and colonization of probiotics is affected by gut microbes.

108

Furthermore, the mechanism of their action on the human body is not well

109

established.

[19]

. Probiotics can be used not only in intestinal

[20]

.

110

Codex Alimentarius provides the definition of dietary fiber: mainly

111

polysaccharides that cannot be digested in the human gastrointestinal tract and are not

112

absorbed by the human. Due to its complexity, the role of dietary fiber has long been

113

controversial. It was once thought that dietary fiber was simply the undigested

114

component of vegetables that promoted bowel movement. Therefore, many people

115

believe that dietary fiber can only control body weight by affecting appetite, energy

116

intake

117

effects on gut microbes

[21]

and thus protect human health. Moreover, dietary fiber also has certain [22]

and reduces the prevalence of Clostridium 4

[23]

. On the

118

contrary, if the intake of dietary fiber is insufficient, the gut balance will be disturbed,

119

the gut microbes will damage the membrane barrier and the infectious diseases will be

120

worsened

121

Bifidobacterium, Lactobacillus abundance and butyric acid increased in the feces of

122

the dietary fiber group: the intervention of dietary fiber (especially fructosan and

123

galactooligosaccharide) increased abundance of Bifidobacteria and Lactic acid

124

bacteria in healthy adult feces, but does not affect its diversity. Based on the above

125

reports, it is clear that dietary fiber can cause changes in gut microbes, thus affecting

126

intestinal health and infectious diseases.

127

High fiber diet on the role and mechanism of various infectious

128

diseases

129

Fiber is not a single substance but rather a heterogeneous group of materials, each

130

with different biologic effects. Cereals, fruits, vegetables, as well as algae, are sources

131

of abundant dietary fiber. Until now, the effects of high-fiber diets on infectious

132

diseases have been controversial. Universally, a low intake of dietary fiber does not

133

only lead to reduce microbial diversity and SCFAs production, but also shifts the gut

134

microbial metabolism toward the utilization of less favorable substrates, particularly

135

dietary and endogenously supplied proteins and host mucins, which maybe

136

detrimental to the host. However, experts differ on the impact of a high-fiber diet on

137

infectious diseases. Human epidemiological studies have shown that eating foods rich

138

in fiber can promote health and thus prevent a series of chronic diseases, especially

139

those related to inflammation

140

positive effect on infectious diseases. However, consumption of certain carbohydrates

141

can promote Listeria infection

142

further aggravate colitis, leading to severe diseases characterized by colon mucosal

143

destruction and massive bleeding

144

metabolic syndrome of t5ko mice, but also can cause liver dysfunction

145

high dietary fiber has side effects on infectious diseases, indicating that the impact of

146

dietary fiber on infectious diseases has a peak, that is, small or excessive amount have

[24, 25]

. Compared with the negative control, the concentration of

[26]

. Dietary fiber may affect gut microbes, and has a

[27]

, and even with CDD supplementation, inulin can

[28]

. Moreover, dietary inulin can improve the

5

[29]

. Certain

147

a poor effect on infectious diseases. The optimal amount of dietary fiber and

148

individualized treatment of dietary fiber will be the focus of future research. At the

149

same time, reintroduction of specific fiber-sensitive taxa may be needed to attenuate

150

intestinal infectious diseases in addition to high-fiber diets remains to be determined.

151

A list of dietary fiber and corresponding pathogens associated with infectious disease

152

is presented in Table 1.

153

6

Dietary fiber

Source

inulin

Chicory root, onion, cereals

cellulose

Cereals, legumes, nuts fructo-oligosaccharides Polymers derived from polysacchar ides by hydrolysis Pectin Fruit peel, legumes, beetroot Galacto-oligosaccharide Garlic, barley, onion, Jerusalem artichoke Hemicellulose Cereals, cell walls of fruits, vegetables 154 155

Active pathogens Listeria

Mode of action

Bifidobacteria, SCFA Lactobacillus , Enterobacter faecalis and C. difficile Salmonella, E.coli, Campylobacer jejuni and Citrobacter rodentium RML prions

Refer ences 27

enhance metabolism

35-46 mucilage degradation of bacteria and repair of intestinal epithelium 55

Salmonella typhi

mucosal immunity

Listeria monocytogens

Intestinal colonisation translocation pathogenic bacterium

colonic microflora

of

and a

Increase stool moisture and faecal bile acid excretion

56

57

58

Table 1 dietary fiber and corresponding pathogens associated with infectious disease

156 157

The underlying mechanisms of dietary fiber on infectious diseases have not been

158

determined. A diet rich in fiber contributes to the maintenance of a healthy gut

159

microbiota associated with increased diversity and functions via the production of 7

160

SCFAs. High fiber intake and the production of SCFAs by the gut bacteria enhance

161

mucus and anti-microbial peptide production, and increase expression of tight

162

junction proteins. In addition, SCFAs reduce oxygen levels and maintain a functional

163

immune system. SCFAs are transported from the intestinal cavity to various tissues

164

where they are used as energy sources, substrates, or signaling molecules to assist in

165

the metabolism of lipids, glucose, and cholesterol

166

attempted to explore the effect of SCFA on infectious diseases. Studies have shown a

167

link among SCFA, intestinal endocrine hormones and glucose homeostasis

168

porcine microbiome analysis, the diet fiber was associated with higher concentrations

169

of Bifidobacteria, Lactobacillus and Enterobacter faecalis, which have protective

170

effects in intestinal inflammation

171

produced by gut microbes fermenting fibers provide energy for the host and play a

172

role in immunomodulation

173

treatment of infectious diseases. Butyrate and propionate are considered as histone

174

deacetylase (HDAC) inhibitors and HDAC regulates the immune system by inhibiting

175

pro-inflammatory macrophage response and dendritic cell differentiation, as well as

176

regulating cytokine expression in T cells

177

secretion of Tregs, IL-10-producing T cells and IL-18 in intestinal epithelial cells by

178

inhibiting HDAC

179

as well as activating NLRP3 that are critical for intestinal environmental stability and

180

epithelial repair

181

homeostasis and immune function

182

exploration. Diets rich in fiber are also associated with increasing mucosal thickness

183

and decreasing mucosal permeability by increasing the secretion of prostaglandin,

184

thereby promoting the expression of epithelial mucin

185

regulate the expression of toxic genes in some pathogens, such as Salmonella, E. coli

186

and Campylobacter jejuni

187

high-fiber diet on infectious diseases is most likely due to the impact of SCFAs on

188

mucilage degradation of bacteria and repair of intestinal epithelium.

189

[38,39]

[41]

[36]

[35]

[30-33]

. Recently, research have

[34]

. In the

and increase the production of SCFAs. SCFAs

. This indicate that SCFAs are beneficial to the

[37]

. Butyrate has been found to increase the

or stimulating GPR109A and GPR43 (GPCRs) signaling [40],

. GPR41 and GPR43 seem to play an important role in metabolic

[44]

[42]

, which deserves further research and

[43]

. In addition, SCFAs can

. The end products of dietary fiber are SCFAs. A

It has also been found that consumption of butyrate by normal colon cells can 8

190

protect progenitor cells in the colon from the effects of high concentration of butyrate,

191

and reduce HDAC inhibition dependent on butyrate and damage to stem cell function

192

[47]

193

SCFA was also related to the immune effect of Treg cells. Recent studies have

194

described the role of SCFAs in the differentiation of T cells into effector cells and

195

regulatory T cells associated with immunity or immune tolerance [49]. The researchers

196

believe that if the host is in a disease-fighting state, SCFA will boost immunity by

197

promoting the differentiation of naive T cells into Th1 and Th17 cells. This study

198

offers new ideas, but more researches are needed to explore the underlying

199

mechanisms.

. SCFA receptor was highly expressed in immune cells

[48]

. We speculated that

200

Fermentation of fiber by gut microbiota yields SCFAs that exert an

201

immunoregulatory role but also provide energy for the host. According to the

202

literature, a subset of dietary fiber sources is fermentable, which means that they serve

203

as growth substrates for microbes in the distal bowel. Some non-digestible

204

carbohydrates have been referred to as “prebiotics,” which are defined as food

205

components or ingredients that are not digestible by the human body but specifically

206

or selectively nourish beneficial colonic microorganisms

207

related to nutrient bioavailability because it combines copper, calcium, and zinc ions,

208

which are released into the distal intestine during fiber fermentation, and these ions

209

play an antibacterial role [51].

[50]

. In addition, fiber is also

210

The second possible mechanism is the succinate theory. Microorganisms produce

211

large amounts of succinate for dietary fiber. Succinate is also an organic acid

212

produced by gut microbes and gut microbes convert it into SCFAs

213

succinate is considered to be a substrate of intestinal gluconeogenesis (IGN), which

214

activates intestinal gluconeogenesis by acting as a glucose precursor. This is a process

215

that improves glucose homeostasis and is beneficial to intestinal health. Dietary fiber

216

can increase succinic acid concentration in the cecum. Prevotella, a known succinic

217

acid-producing bacterium, improves glucose homeostasis by communicating with the

218

host through an unknown mechanism [54]. In this area, almost all studies have pointed

219

to the function of SCFA, but few have studied other mechanisms. The succinate 9

[52,53]

. Dietary

220

theory is a new discovery in recent years. Although there are still many imperfect

221

hypotheses, it is a new idea and method, which is beneficial to future research.

222

Effect and mechanism of single or combined probiotics on infectious

223

diseases

224

According to available literature, the concept of fermented milk existed in Middle

225

East a long time before the era of Phoenicia. During the early 7000 BC, the traditional

226

foods of the Egyptians like Laban Khad and Rayeb were prepared through the

227

fermentative action of bacteria what we now know as probiotics. Current research

228

shows that the role of probiotics is more in preventing pathogen infection,

229

maintaining intestinal barrier or immune regulation, rather than colonization

230

characteristics. Research on probiotics in infectious diseases has made great progress

231

in recent years. Lactobacillus casei has anti-inflammatory effects on human intestinal

232

epithelial cells infected by Shigella infection

233

pro-inflammatory cytokines mainly through toll-like receptor. Moreover, probiotics

234

can prevent and treat diarrhea caused by viral and bacterial infections

235

prevented C. difficile infection

236

supplementation of Lactobacillus GG (LGG) to children reduced the incidence of

237

HRV disease [61]. In oral flora, probiotics can attach to the tooth surface and blend into

238

the bacterial community that forms dental biofilm, compete with and antagonize

239

caries causing bacteria, thus preventing their proliferation

240

current major clinical applications of probiotics are antibiotic-related diarrhea and C.

241

difficile infection. There’s a general belief among the public that consuming probiotics

242

can edge out “bad” bugs and promote gut health even in healthy people. But one

243

major failing is a lack of randomized trials that sufficiently report safety data for

244

probiotics. Although probiotics are beneficial for infectious diseases in animal

245

experiments, probiotics should not be used indiscriminately in general. The

246

effectiveness and safety of probiotics cannot be solely based on animal experiments,

247

large-scale clinical experiments are a more reliable method.

248

[60]

[58]

. Probiotics reduce the expression of

[59]

. Probiotics

and in randomized clinical studies, prophylactic

[62-65]

. Taken together, the

Probiotics combined with other antibiotics can also be more effective in treating 10

249

and preventing infectious diseases than even single probiotic. Probiotics plus

250

antibiotics had a lower risk of adverse reactions (such as abdominal cramps and

251

nausea) when combined with probiotics versus placebo or no treatment

252

additional benefit was observed in commercial multicomponent mixtures of probiotics,

253

it was useful to assess the impact of more specific combinations such as Lactobacillus

254

casei and Bacillus brevis mixtures. Strain specificity can lead to anti-pathogen activity,

255

so the appropriate combination of strains can lead to synergistic effects [67]. When

256

used in combination with three probiotics, prebiotics significantly reduced

257

Campylobacter infection

258

mixed with antibiotics also play a role in infectious diseases. Probiotics and

259

antibiotics are co-administered by biofilm encapsulation, providing dual bactericidal

260

capabilities, and as a new way to treat complex infections and overcome antibiotic

261

resistance. A list of probiotics and corresponding pathogens associated with infectious

262

disease is presented in Table 2.

[68,69]

[66]

. While no

. In addition to combination of probiotics, probiotics

263

11

Probiotics Lactobacillus casei LGG

Active pathogens Shigella bacteria HRV

mode of action Reduce the expression of pro-inflammatory cytokines

the probiotic Salmonella bacteria blend

key reference[s]

58-61

intestinal immune regulation 71-75

Lactobacillus royale Lactobacillus and Yersinia Bifidobacterium

antagonism

Lactobacillus Candida albicans rhamnosus L60 and and Streptococcus Lactobacillus lactis fermentans L23 Bifidobacteria and Campylobacter Saccharomyces jejuni and cerevisiae Staphylococcal septicemia Lactobacillus and Campylobacter Bifidobacterium jejuni and Listeria

competitive exclusion

76-78

79 inhibit the colonization of pathogens

80-84

reducing the virulence of pathogens

85-87

Table 2 probiotics and pathogens associated with infectious disease

264 265 266

A broad overview of common mechanisms in the probiotics includes settlement

267

resistance, acid production, SCFAs, regulation of intestinal transport, normalization of

268

disturbed

269

immunomodulation and competitive rejection of pathogens

270

colonization mechanism of probiotics can help develop "personalized" flora therapy.

271

Probiotics confer immunological protection to the host through the regulation,

272

stimulation, and modulation of immune responses. Mucosal immunity is the most

273

important in the intestinal immunomodulation. Probiotics prevent Salmonella from

274

inducing lymphocyte proliferation through innate immune regulatory mechanism

275

[71,72]

276

and dendritic cells. The presence of probiotics restored the migration of lymphocytes

microbial

communities,

increasing

intestinal

cell [70]

turnover,

. Studying the

. Probiotics mainly act on innate immune cells such as lymphocytes, neutrophils

12

277

and dendritic cells in intestinal mucosal tissues, thereby inhibiting Streptococcal

278

infection. During infection with Salmonella and Pseudomonas aeruginosa, the

279

maturation and secretion of IL-1β occurs immediately through NLRC4, which are

280

expressed in intestinal phagocytes

281

additional effects on the induction of dendritic cell maturation and IL-10 cytokines

282

expression

283

tryptophan produced by Lactobacillus royale induce the development of regulatory

284

CD4+CD8α+ double positive lymphocytes [75]. In all, the effectiveness of probiotics in

285

prevention and treatment is dependent on several factors such as class or strains of

286

probiotics, the dosage of probiotics, and heterogeneity of study subjects. These

287

probiotics modulate the pathogenesis of infectious diseases and protective immunity

288

against pathogens in species and strain specific manner. Collectively, it appears that

289

the selected G- probiotics is more effective than the various tested G+ probiotics in

290

enhancing protective immunity.

[74]

[73]

. The combination of G+ and G-probiotics has

, which may play a role in enhancing the IgA response. In addition,

291

Another possible mechanism is the antagonism of probiotics against pathogens.

292

Lactobacillus and Bifidobacterium play a key role in regulating gut microbes and

293

maintaining host health

294

enterocolitis. For pathogens such as Yersinia, the potential therapeutic mechanism is

295

the activation of urease, which catalyzes the hydrolysis of urea to produce toxic

296

metabolites

297

Lactobacillus on urease activity by evaluating the ability of pathogen groups derived

298

from cocultures to hydrolyze urea and release ammonia in urease analysis. In vitro,

299

Lactobacillus could inhibit the growth of Yersinia enterocolitis [78].

[77]

[76]

, and they can antagonize Yersinia urea plasma

. Therefore, the experimental group monitored the effect of

300

The most well-known effect of probiotics is competitive exclusion, which is

301

widely known as the most basic application of probiotics. Competitive inhibition

302

refers to probiotics can competition pathogen survival environment that not only

303

nutrients needed for the survival of pathogenic bacteria. These probiotics are

304

described to have antimicrobial properties. Studies have shown that bacteriocin like

305

substances produced by Lactobacillus rhamnosus L60 and Lactobacillus fermentans

306

L23 have antibacterial activity against Candida albicans and Streptococcus lactis [79]. 13

307

Probiotics may elicit their beneficial effects against pathogens through inhibiting

308

the colonization of pathogens. A role for probiotics (Bifidobacteria and

309

Saccharomyces cerevisiae) in mediating host defenses against infectious diseases

310

including Campylobacter jejuni and Staphylococcal septicemia

311

permeability of intestinal mucosa includes adhesion, internalization and translocation,

312

which is mediated by flagellum movement and adhesion elements

313

established that probiotics competitive inhibition of pathogens by improving the reach

314

speed, competitive exclusion and preference site on intestinal epithelial cell adhesion

315

sites, luminal PH change, producing bacteriocin, strengthening the tight junction

316

protein, adjusting the immune system, quorum sensing, and enhancing bacterial

317

crosstalk.

[84]

[80-83]

. The

. It is also well

318

Other studies have shown that probiotics can prevent and treat intestinal

319

infections by reducing the virulence of pathogens. Lactobacillus and Bifidobacterium

320

reduced colonization of the intestinal wall by pathogenic bacteria and also showed

321

that probiotics may reduce the toxicity of Campylobacter jejuni and Listeria

322

However, some results showed that Lactobacillus could not reduce Listeria

323

monocytogenes infection in caco-2 cells, so whether the reduced virulence of

324

probiotics on Listeria was due to the effect of probiotics or the adhesion protein of

325

Listeria remained to be further investigated.

[85-87]

.

326

These results underscore that the benefits of synergistic bacterial mixtures can be

327

broadly attributed to any of three mechanisms: interference with the growth or

328

survival of pathogenic microorganisms in the gut, improvement of mucosal barrier or

329

mucosal immune system, and get through systemic immune system and influence

330

other organs outside the gut [88-90]. At the same time, it should be noted that the results

331

of animal experiments may not be applicable to humans. When considering the role of

332

strains, it is also necessary to fully consider that metabolites may also be effective.

333

More rigorous and in-depth clinical researches are needed in the future, but similar

334

treatment time, comparatively significant probiotic strains, and effective response to

335

different types of vaccines need to be applied. 14

336

Conclusion and perspectives

337

Although antibiotics are commonly used to treat infectious diseases, emergence of

338

antibiotic resistant strains highlights the necessity for developing novel alternative

339

approaches. We emphasized in this review the effects of the dietary fiber and

340

probiotics on infectious diseases. Dietary fiber and probiotics are both readily

341

available on a daily basis, and most studies have revealed that dietary fiber and

342

probiotics have positive effects on infectious diseases. Therefore, dietary fiber and

343

probiotics have prophylactic and therapeutic potential with respect to infectious

344

diseases. However, due to the structural complexity of dietary fiber, the diversity of

345

probiotics types and the host specificity of probiotic colonization, there are still a long

346

way to go before dietary fiber and probiotics move from basic research to clinical

347

application.

348

In terms of dietary fiber, studies have investigated that different concentrations

349

of dietary fiber have different or even opposite effects on human health.

350

Recommended dietary reference intake (DRI) for dietary fiber is consumption of 25 g

351

for adult women and 38 g for adult men, based on a 2000 kcal/day diet [91]. Although

352

studies conducted in healthy populations have shown that 10 g of prebiotics (mainly

353

FOS, oligofructose, and inulin) can reduce diarrhea

354

infectious disease have not been properly determined. In clinical patients，the

355

administration frequency of dietary fiber and probiotics is still less progress. At the

356

same time, the time of positive effect last after cessation of use of probiotics/dietary

357

compounds and the side effect (abdominal distension) are controversial [93,94]. In total,

358

the human fight against infectious diseases has never been stopped.

[92]

, the therapeutic dosage for

359

The efficacy of probiotics is controversial, and there are no approved probiotics

360

in Europe and America. Despite some clinical studies to date, the use of dietary fiber

361

and probiotics for drug therapy is not recommended due to insufficient data

362

supporting the efficacy of dietary fiber and probiotics in prophylaxis or treatment, and

363

conflicting reports of benefits. Secondly, the impact of excessive dietary fiber on the

364

human body is uncertain, and the negative effects of probiotics have not been 15

365

carefully studied, so the basic experiment is not complete. Moreover, the host's

366

immune system is so complex that the biological activity in basic research does

367

not fully compatible with the human body. Although, these studies provide very

368

interesting insights into the concept of personalized probiotics approach, as they could

369

predict gut colonization based on participant characteristics.

370

Probiotics are increasingly considered to be potential preventive and even live

371

biotherapeutic tools to counterbalance gut microbiota dysbiosis encountered in human

372

infections. Probiotics have many benefits for combating infectious diseases, but they

373

are not commonly used to treat patients for their efficiency and security. Improving

374

the efficacy of probiotics requires overcoming colonization resistance of the host flora,

375

developing disease- or population-specific interventions, and conducting large-scale

376

randomized double-blind clinical trials without commercial interest. To date, the

377

clinical application of probiotics is mainly to treat diarrhea in children through

378

regulating gut microbiota dysbiosis. However, these promising approaches require

379

further research and validation about usefulness and security. The research will focus

380

on understanding the mechanism behind the colonization tendency of probiotics in

381

individuals, and considering more factors such as the dosage, duration of efficacy,

382

biofilm formation, ecological rejection, and the negative effects of probiotics, which

383

will help to develop “personalized” probiotic therapy and apply to clinical.

384

Overall, future research on probiotics and dietary fiber will focus on

385

individualized research, combined with clinical practice, combining clinical parameter

386

assessment with gut microbiota research rather than animal experiment. It is believed

387

that through further systematic research, the role of dietary fiber and probiotics in the

388

relationship between bacteria and infectious dysfunctions will be clearer and

389

ultimately benefit the public.

390

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