Diets intervene osteoporosis via gut-bone axis

Figures & data

Figure 1. Interactions and connections between the gut microbiota and its metabolites with multiple organs and tissues of host. Several factors, such as exercise, medication, diets, pollution, age and gender, genotype and so on, might affect the gut microbiota and its metabolites of population, and then cause corresponding changes to the bone, liver, brain, heart, kidney, pancreas, lung, and other organs of the host via a variety of regulation approaches. LPS, lipopolysaccharide; BAs, bile acids; SCFAs, short chain fatty acids; TMAO, trimetlylamine oxide.

Figure 2. Association between gut microbiota and osteoporosis based on the gut-bone axis. Specifically, gut microbiota can regulate metabolic, immune, and inflammatory states of the body. Meanwhile, it can serve as a pivotal regulatory factor in the bone metabolism, regulating the immune system, affecting the generation of osteoclasts, and exerting regulatory effects on the bone. Studies on the regulation of inflammatory factors and hormones in the gut microbiota have shown that anti-inflammatory factors can reduce bone resorption and prevent bone loss. The constantly emerging researches on probiotics regulating bone metabolism has revealed that the increase of beneficial microbiota can promote the enhancement of bone mass and serve as a potential target for preventing and treating osteoporosis. However, the researches on the relationship between gut microbiota and osteoporosis is still in its infancy, and various studies are needed to further clarify its underlying mechanisms of action. TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; IL-6, interleukin-6; SCFAs, short chain fatty acids; 5-HT, 5-hydroxytryptamine; NF-kB, nuclear transcription factor-κB; ca, calcium; vit D, vitamin D; SFB, segmented filamentous bacteria; LPS, lipopolysaccharide; GLP-1, glucagon-like peptide-1; IFN-γ, interferon-γ; TGF-β, transforming growth factor-β; GIP, glucose-dependent insulinotropic polypeptide; OPG, osteoprotegerin; RANKL, receptor activator of nuclear factor-kB ligand; RANK, receptor activator of nuclear factor-kB; ZO-1, zona occludens 1; ALP, alkaline phosphatase; CINP, N.Terminal propeptide of type I collagen; CTX-1, C-terminal telopeptide of type I collagen; IGF-1, insulin-like growth factor-1; TRACP-5b, tartrate-resistant acid phosphatase 5b.

Figure 3. The effects of dietary nutrients on osteoporosis by acting on gut microbiota and its metabolites. Under the domination of various dietary patterns, gut microbiota is closely related to the synthesis and absorption of essential nutrients, such as protein, vit D, ca, P, and mg, which affect the intestinal mucosal barrier function, intestinal inflammation, metabolites, etc., thereby participating in the modulation of the balance between bone formation represented by osteoblasts and bone absorption represented by osteoclasts via systemic circulation. SCFAs, short chain fatty acids; vit D, vitamin D; ca, calcium; P, phosphorus; mg, magnesium; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β; IL-6, interleukin-6; NF-kB, nuclear transcription factor-κB; LPS, lipopolysaccharide; CRP, C-reactive protein; OPG, osteoprotegerin; ALP, alkaline phosphatase; CINP, N.Terminal propeptide of type I collagen; RANKL, receptor activator of nuclear factor-kB ligand; RANK, receptor activator of nuclear factor-kB; CTX-1, C-terminal telopeptide of type I collagen; ZO-1, zona occludens 1; TRACP-5b, tartrate-resistant acid phosphatase 5b.

Figure 4. Different dietary patterns on osteoporosis by modulating the gut microbiota and its metabolites. Different dietary nutrients (such as protein, fat, carbohydrates, etc.) and different dietary patterns (such as Western diet, vegan diet, mediterranean diet, etc.) may affect gut microbiota and its metabolites, and the changes of gut microbiota and its metabolites may also influence the metabolic status of host, thereby adjusting the bone metabolism and modulating the occurrence and development of osteoporosis. The effects of different dietary patterns on gut microbiota and bone metabolism are exhibited in this figure.

Table 1. The effects of different dietary patterns on gut microbiota, metabolites, and bone health.

Dietary patterns	Dietary characteristics	Affected microbiota and metabolites	Impacts on gut and bone	Involved mechanisms
Western diet^Citation97–100	High in calories, fat, and proteins Low in carbohydrates and dietary fiber	↑Firmicutes, Clostridium, Acetitomaculum, Faecalibacterium ↓Bacteroides	Increase the absorption of calories from food Promote fat synthesis and accumulation Alleviate insulin resistance and chronic inflammation Damage the intestinal mucosal barrier and enhance intestinal permeability Damage to bone tissue and endanger bone health	Modulate the composition, abundance, and diversity of gut microbiota Reduced SCFAs (specifically propionic acid and butyric acid) Elevated LPS in circulation
Mediterranean diet^Citation101–103	Appropriate calories, fats, and proteins High in whole grains and dietary fiber	↑Prevotella, Bacteroides, Enterococcus, Lactobacillus, Bifidobacterium ↓Clostridium	Inhibit the synthesis of cholesterol and fat Promote cholesterol excretion through feces Alleviate insulin resistance and chronic inflammation Maintain the intestinal integrity Optimize overall metabolic status and improve bone health	Enhanced SCFAs (specifically acetic acid, propionic acid, and butyric acid) Reduced LPS in circulation Increased contents of beneficial microbiota
Vegan diet^Citation104–107	No intake of animal derived foods Proper calories, fats, proteins, and carbohydrates High in dietary fiber	↑Prevotella, Xylanibacter ↓Enterococcus, Bifidobacterium	Reduce the absorption of calories in food Inhibit the synthesis of cholesterol and fat Promote cholesterol excretion through feces Alleviate insulin resistance and chronic inflammation Maintain the intestinal integrity The intake of vegan diet is positively correlated with an increase in BMD in population, while the absolute vegetarians have lower BMD and higher risk of fractures, and it is necessary to ensure sufficient intake of calcium, vit D, and protein	Modulate the composition, abundance, and diversity of gut microbiota Enhanced SCFAs (specifically acetic acid, propionic acid, and butyric acid) Reduced LPS in circulation
Anti-inflammatory diet^Citation108–111	Mainly based on plant-based foods, with abundant intake of dietary fiber High in whole grains, omega-3 fatty acids, and spices	↑Faecalibacterium prausnitzii, Lactobacillus, Bifidobacterium, Prevotella, Bacteroides ↓Acidaminococcus, Clostridium	Reduce the absorption of calories in food Alleviate insulin resistance and chronic inflammation Provide a variety of antioxidants Inhibit the synthesis of cholesterol and fat Reduce the negative impacts of inflammation on bone health	Enhanced SCFAs (specifically acetic acid, propionic acid, and butyric acid) Reduced LPS in circulation Increased contents of beneficial microbiota
Ketogenic diet^Citation112–114	High fat, low carbohydrate, and moderate proteins	↑Lactobacillus, Akkermania mucophilus, Actinomycetes, Parabacterium ↓Bifidobacterium, Escherichia, Salmonella, Vibrio, Escherichia coli, Shigella	Insufficient intake of dietary fiber, essential vitamins, and minerals Promote weight loss, improve blood sugar control, and enhance metabolic efficiency The impacts of ketogenic diet on bone health is still controversial	Modulate the composition, abundance, and diversity of gut microbiota Enhanced SCFAs (specifically butyric acid)
Korean diet^Citation115–117	High protein, multi vegetable, light and non-greasy, with a predominantly cool and spicy taste	↑Firmicutes, Weissella, Coprococcus, Ruminococcus, Oscillospira, Gemmiger, Blautia, Coprococcus ↓Bacteroidetes	Reduce the pH value of intestine Inhibit the synthesis of cholesterol and fat Reduce the absorption of calories in food Excessive salt and saturated fat intake have negative impacts on bone health	Enhanced SCFAs (specifically acetic acid, propionic acid, and butyric acid) Increased contents of beneficial microbiota
Intermittent diet^Citation118	Control meal times to improve body composition and overall health, including restricted fasting, overnight fasting, and religious fasting	↑Akkermania mucophilus, Paralactobacillus ↓Escherichia coli, Turicibacter	Maintain the intestinal integrity Relieve LPS leakage and systemic inflammatory response Improve metabolic status and reduce risk of obesity and obesity-related diseases Improve bone health by enhancing the abundance and diversity of beneficial microbial communities, while there is still a lack of sufficient research evidence to support	Modulate the composition, abundance, and diversity of gut microbiota Enhanced SCFAs (specifically acetic acid, propionic acid, and butyric acid) Reduced LPS in circulation

SCFAs, short chain fatty acids; LPS, lipopolysaccharide; BMD, bone mineral density; vitamin D.

Figure 5. Different impacts on bone by modulating gut microbiota and its metabolites under different dietary recommendations. The reasonable dietary patterns integrate the characteristics of healthy dietary patterns, such as a Mediterranean diet and an anti-inflammatory diet, mainly including the diversified food, high fiber intake, low sugar intake, low fat intake, and high grains intake, thereby maintaining the bone health and preventing osteoporosis. On the contrary, unhealthy dietary pattern (such as Western diet), represented by high-fat, high sugar, high salt, and high calorie dietary intake, is not conducive to maintaining the intestinal and bone health. SCFAs, short chain fatty acids; TMAO, trimetlylamine oxide; TMA, trimethylamine; LPS, lipopolysaccharide; TNF-α, tumor necrosis factor-α; CRP, C-reactive protein; IL-10, interleukin-10; IL-1β, interleukin-1β.

Guo Y, Luo S, Ye Y, Yin S, Fan J, Xia M. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. J Clin Endocrinol Metab. 2021;106(1):64–79. doi:10.1210/clinem/dgaa644.

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